The objective of the present study was to develop floating microsphere of norfloxacin 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, HPMC K15M) and ethyl cellulose with drug in the mixture dichloromethane and ethanol at ratio of (1:1) with tween 80 (stabilizing agent). FTIR study shows that drug and other excipients are compatible with each other. The effects of polymer concentration on drug release profile were investigated. A 33 centrecomposite design was applied to systemically optimize the drug release profile. Polymer to drug ratio; HPMC K4M (X1), HPMC K15M (X2) and stirring speed (X3) were selected as independent variables. The floating microspheres were characterized by the results obtained as percentage yield, percentage buoyancy and in-vitro drug release was studied for 12 hour. The Surface morphology studied by scanning electron microscopy and Accelerated stability study was performed for three months indicated that optimized formulation was stable. The floating microspheres showed better result and it may be useful for prolong the drug release in stomach and improve the bioavailability.