INTRODUCTION: Diabetes mellitus (DM) has become a global epidemic with prevalence of 300-600 million diabetic persons. Of them 90-95% suffer from Type 2 diabetes mellitus (T2DM). Obesity, sedentariness, and lack of physical activity are the risk factors in the occurrence of T2DM. It causes multi-systemic complications in the human body and it is considered among the few top listed chronic diseases with significant morbidity and mortality and economic challenge and burden on the global health care system. Physical activity and exercise, on the other hand, have a key role in the prevention and management of both at risk and diagnosed patients with T2DM. Physical activity, exercise and diet control are the key components of lifestyle modifications commonly used along with medical management for T2DM. PURPOSE: The present study was designed with the objectives to determine the effect of Supervised, Structured Aerobic Exercise Training (SSAET) Programme, combined with routine medication and dietary plan on Fasting Blood Glucose Level (FBGL), Plasma Insulin Level (PIL) , Glycemic Control (GC), Insulin Resistance (IR) , Interleukin-6 (IL-6) , Nitric Oxide Synthese-1 (NOS-1), Cyclooxygenase 2 (COX2), High Density Lipoprotein (HDL) , Low Density Lipoprotein (LDL), Rate of PerceivedExertion (RPE), Dyspnea Index (DI), Maximal Oxygen Consumption (VO2max), and Body Mass Index (BMI). MATERIAL AND METHODS: This randomised controlled trial was conducted at Riphah Rehabilitation and Research Centre (RRRC), at Pakistan Railways General Hospital (PRGH), Rawalpindi, which is a clinical training health care centre of Riphah International University, Islamabad. The duration of my study was 18 months from 1 January 2015 to 30 June 2016. Inclusion criteria were male and female patients of age 40-70 years with minimum one year history of T2DM after diagnosis as per WHO criteria. Patients with the previous history of chronic systemic diseases, smoking, regular exercise and diet plan were excluded. Sample size was calculated by pilot study (n=20) and Epitools, an online sample size calculator was used. A total of 195 patients were screened out as per inclusion criteria. Of them 120 fulfilled the criterion. Finally 102 agreed for enrolment and participation in the study, which were then randomly placed into experimental (n=51) and control (n=51) groups by lottery methods. SSAET was applied to experimental group along with routine medication and dietary plan for 25 weeks, at 3 days per week. Likewise the control group was managed with routine medication and dietary plan for 25 weeks. The study outcome measures were FBGL, PIL, GC, IR, IL-6, NOS-1, COX2, HDL, LDL, RPE, DI, VO2max, and BMI. Assessments of all outcome measures were done at baseline and on the completion of 25 weeks intervention period. Prior approval of the study was taken from Institutional Review Board at the University of Lahore and written consent was also taken from all participants in Urdu before their enrolment in the study. Intervention in the form of aerobic exercises was applied to experimental group through medically graded treadmill along with routine medication and dietary plan. A telemetric monitoring of Blood Pressure (BP), Heart Rate (HR) and Electrocardiography (ECG) was done. The 25 week SSAET programme was divided into 5 phases of 5 weeks duration each and exercise time was 10-minute per session in phase one and 30 minutes per week. A 10-minute increase per session was followed in all subsequent phases from 2-5. Inclination on the treadmill with the ground was zero in phase-1 and 3 degrees in phase-2 while 3 degrees increase was done in phase 3-5 degree. Normal individual speed was used as treadmill speed and calculated by 20 meter distance test. Control group was managed by routine medication and dietary plan. All laboratory investigations were conducted at multidisciplinary research lab at Islamic International Medical College (IIMC), constituent institute of Riphah international university Islamabad, Pakistan. Data was analyzed using SPSS software version-20. RESULTS: The mean age of the participants was 54.73 + 8.17 years with 53.73 + 8.70 years in experimental group and 54.98 + 7.63 years in control group. The male and female participants (66.7%) were 68 and 34 respectively. Sixty four participants (62.74%) were jobless and 37.25% (38) were doing jobs. Most of the participants were married 97.05% (99) and 2.94% (03) were unmarried. Mean years of history with diabetes were 7.12 + 4.32 years ranging from 1-16 years. Regarding the past history of exercise, only 17 (16.66%) had history of exercises and 85 (83.33%) had history of sedentariness.Thirty two (31.37%) had past history of diet control while 70 (68.62%) had no previous history of diet control. Family history of DM was positive among 64 (62.5%) and negative in 38 (37.25%) of the experimental group. As long for the post diabetic complications were concerned, only 26 (25.49%) showed musculoskeletal complications and 76 showed no post-diabetic musculoskeletal complications. SSAET programme, routine medication and dietary plan managed the FBGL (premean=276.41 + 25.31, post-mean=250.07 + 28.23), PIL (pre-mean=13.66 +5.31, post mean=8.91 +3.83), GC (pre-mean=8.31 +1.79, post mean=7.28 + 1.43), IR (pre-mean= 64.95 + 27.26, post-mean= 37.97 + 15.58), IL-6 (pre-mean= 0.25 + 0.11, post-mean=0.19 + 0.04), NOS-1 (pre-mean=4.96 + 1.06, post-mean=3.01 + 1.39), COX2 (pre-mean=18.72 + 4.42, post-mean=15.18 +2.63), LDL (pre-mean=118.56+19.17, post mean= 102.64+13.33), HDL (pre-mean=42.70+8.06, post mean=47.47+7.16), LOE (pre-mean=10.56+1.62, post mean=07.39+1.40), Dyspnea (pre-mean=14.88+1.99, post mean=11.25+2.28), vo2max (premean=36.90+2.78, post-mean= 40.11+3.30), and BMI (pre-mean=29.95+5.31, postmean=27.73+4.84) more significantly as compared with the control group treated with routine medication and dietary plan. The control group showed non-significant results in FBGL (pre-mean= 268.19 + 22.48, post-mean= 281.41 + 31.30), PIL (pre-mean=14.14 + 5.48, post-mean=14.85 + 5.27), GC (pre-mean=8.15 + 1.74, post-mean=8.20 + 1.44), IR (pre-mean64.49 + 23.63, postmean=70.79 + 23.30), IL-6 (pre-mean=0.23 + 0.08, post mean=0.27 + 0.08), COX2 (premean= 18.49 + 4.56, post-mean=19.10 + 4.76), LOE (pre-mean=10.54+1.60, postmean=12.07+1.16), Dyspnea (pre-mean=14.52+2.42, post-mean=16.29+2.38), and BMI (premean=29.93 + 4.92, post-mean=30.10+5.06), while two variables NOS-1 (pre-mean= 4.63 + 1.61, post-mean=4.31 + 2.06) and VO2max (pre-mean= 38.00+3.26, post-mean=37.13+3.04) demonstrated significant improvements. CONCLUSIONS: Based on the results of the current study it is concluded that SSAET programme is a better option for physical therapists and other clinicians to manage Patients with T2DM, along with routine medication and dietary plan, including higher blood glucose level, insulin resistance, low grade inflammation, deranged lipid profile and weak physical condition.