The aim and objective of the study was to develop and evaluate biodegradable polymer drug delivery system that is capable of extended the drug release for prolong period of time at predetermined rate and being a free flowing solution at room temperature and converts to gel with increase in temperature. In the current study four polymers (Poloxamer 407, Methyl cellulose, Hydroxypropyl methylcellulose and polyethylene glycol) were used alone and in combination with each other in different ratios. Pluronic PF-127 (Poloxamer 407) and methylcellulose (MC) gels below 37oC at appropriate concentrations (P= 18% w/v, 20%w/v, MC=4%w/v, PM=15/3%w/v, MPG3/2w/v and MPG1.5/10% w/v). To evaluate the efficacy of the in-situ thermoreversible formulations in controlling the drug release three drugs diclofenac sodium (hydrophobic), timolol maleate (hydrophilic) and insulin (protein) were selected. The in-situ gels were evaluated for their physical properties like Tsol-gel, viscosity, clarity of solution and gel. The drug delivery system was also evaluated for drug content, in-vitro drug release and pharmacokinetic parameters were also determine with in-vivo studies. The data obtained for drug content after autoclaving the solutions indicates that autoclaving results in degradation of DS while it has no significant effect on TM.To predict the drug release kinetics and mechanism various mathematical models were applied to the in-vitro dissolution data. To predict the pharmacokinetic parameters Pk- Summit software was used. Based upon the in-vitro and In-vivo data it was concluded that the system consisting of the poloxamer 407 in concentration of 20% (DP20 and TP20) are the most capable formulation for extending the drug release and maintaining therapeutic blood level of DS and TM for longer duration. While the formulation IPM15/3 consisting of 15%w/v poloxamer 406 and 3% MC w/v retarded the drug release and maintaining the plasma insulin in steady state for longer duration of time. The results obtained in current study suggests that the HPLC-UV method developed is sensitive and rapid method for the determination of DS and TM in pharmaceutical preparation and physiological fluids (plasma, AH). The data also suggests that the studied polymers Poloxamer, MC and PG are good candidate to extend the drug release possessing a unique thermoreversible property. The physical data obtained during the experimental work indicates that the studied in-situ thermorevesible sol-gel formulations were capable to retard the release of these drugs. The drug delivery systems were smart enough to be used for the administration of the studied drugs through subcutaneous and ophthalmic routes.