The main objective of the present work was to develop a formulation with increased therapeutic efficacy, reduced frequency of administration and improved patient compliance by developing sustained release microspheres of Lamivudine using different polymers to study its functionality for sustained release of drug from microspheres formulations. Different concentrations of polymers like sodium alginate, HPMC, sodium CMC, chitosan was selected for the study. Microspheres were prepared by using ionic- gelation method. Prepared microspheres were evaluated for particle size, flow properties, drug content, entrapment efficiency. After evaluation of physical properties of microspheres, the in vitro release study was performed in 0.1 N HCl as buffer for 2 hrs. after that replace with 6.8 phosphate buffer up to 8hrs. After 8 hrs. of study microspheres with sodium CMC showed maximum release (88.2%). Among all the formulations F7 which contain 200 mg of sodium CMC release the drug which follows first order kinetics. The optimized formulation of sodium CMC (F7) was subjected to stability with respect to release pattern.