The objective of the present study was to develop floating microspheres of Captopril in order to achieve an extended retention in the upper GIT which may enhance the absorption and improve the bioavailability. The microspheres were prepared by solvent evaporation method using different ratio of hydroxyl propyl methyl cellulose (HPMC K4M) with drug in the mixture dichloromethane and ethanol at ratio of (1:1), with tween80 as the surfactant. Differential Scanning Calorimeter (DSC) study shows that drug and other excipients are compatible with each other. The effects of polymers concentration on drug release profile were investigated. A 32 full factorial design was applied to systemically optimize the drug release profile. Polymer to drug ratio (X1) and stirring speed (X2) were selected as independent variables. The floating microspheres were characterized by and results obtained are % yield, particle size analysis, drug entrapment efficiency, buoyancy percentage, in-vitro drug release was studied for 12 hour and scanning electron microscopy. Accelerated stability study was also performed for three months indicated that optimized formulation was stable. The floating microspheres showed better result and it may be use full for prolong the drug release in stomach and improve the bioavailability.