T2DM (Type 2 diabetes mellitus) is an endocrine disease having a significant genetic component.Polymorphisms of many genes may affect hereditary vulnerability of the disease that is characterized by insulin resistance and islet disorder. Though numerous factors associated with diabetes mellitus (DM) within local population have been assessed but gaps exist in determining genetic elements that contribute to this disease. As the genetic basis of T2DM can vary between ethnic groups, it is important to investigate the genetic link of T2DM in Pakistani populace. The existing project was aimed to assess the association of receptor for advanced glycation endproduct (RAGE) gene polymorphism (-429T>C and -374T/A) with type 2 diabetes mellitus within local populace. It employed 50 normal individuals and 100 patients suffering from type 2 diabetes mellitus (T2DM). Case control study involved demographic features and relative analysis associated with biochemical parameters (fasting blood sugar, HbA1C (glycated hemoglobin), liver function tests, lipid profile, renal function tests) within normal and diabetic individuals. Genotyping of the RAGE gene was studied by PCR- RFLP on genomic DNA. Among baseline characteristics, body mass index and blood pressure were notably (p<0.01) greater in case subjects in comparison with normal participants. Blood glucose, glycated hemoglobin and lipid profile showed substantial difference (p<0.01) between case and control subjects. Biochemical parameters had insignificant (p>0.01) relation with both genetic variants. Additionally RAGE gene polymorphism had non-significant association (p>0.05) with post diabetic complications. It is suggested that there might be no association of RAGE gene variants -429T>C and -374T/A with T2DM, diabetic retinopathy, nephropathy, cardiac and hypertensive manifestations in Pakistani population. To date this is the first national study as per our knowledge that throws light on the association of RAGE gene variants with T2DM and various biochemical parameters. Therefore, further exploration is needed to comprehend molecular and cellular systems of polymorphism which is still ambiguous. Additionally more genetic investigations might identify new candidate genes for treatment and prevention of the disease.