The present study involves preparation and evaluation of floating microspheres with Metformin Hydrochloride as model drug for prolongation of gastric residence time. The microspheres were prepared by the emulsification solvent diffusion technique using polymers Hydroxypropylmethyl cellulose K4M and Eudragit RS100. The shape and surface morphology of prepared microspheres were characterized by scanning electron microscopy, respectively. In vitro drug release studies were performed and drug release kinetics was evaluated using the linear regression method. Effects of the stirring rate during preparation, polymer concentration, solvent composition and dissolution medium on the size of microspheres and drug release were also observed. The prepared microspheres exhibited prolonged drug release (8 h). The mean particle size increased and the drug release rate decreased at higher polymer concentration. No significant effect of the stirring rate during preparation on drug release was observed. In most cases good in vitro floating behavior was observed and a broad variety of drug release pattern could be achieved by variation of the polymer and solvent ratio, which was optimized to match target release profile. The developed floating microspheres of metformin hydrochloride may be used in clinic for prolonged drug release in stomach for at least 8 hrs, thereby improving the bioavailability and patient compliance.