Glipizide microspheres were prepared by solvent evaporation method using different concentrations of Eudragit RS 100 as matrix polymer along with dibutyl phthalate and diethyl phthalate as plasticizers. Prepared microspheres were evaluated for percent drug content, encapsulation efficiency, micromeritic properties, in vitro drug release and characterized for scanning electron microscopy and fourier transforms infrared spectroscopy. Microspheres formed were spherical with smooth surface showing cross linking by physical observation. Increased concentration of Eudragit RS 100 and plasticizers has increased percentage entrapment efficiency and also improved the micromeritic properties of the microspheres. Increased plasticizer concentration has sustained the drug release with probable mechanism of diffusion was homogenous matrix as it followed the Higuchi model.