The objective of the present study was to develop floating microspheres of Levofloxacin hemihydrate for the treatment of peptic ulcer disease caused by Helicobacter pylori (H. pylori). Levofloxacin hemihydrate was chosen as a model drug because it preferentially absorbed from the upper part of the gastrointestinal tract. The floating microspheres were prepared by the emulsion solvent evaporation method using polymers hydroxypropylmethylcellulose (HPMC K4M) in fixed ratio and Ethylcellulose in variable ratios, in the mixture of acetone and ethanol at ratio of (1:1), with tween80 as the surfactant. 23 factorial design was adopted to optimize the formulation variables. The floating microspheres were evaluated for Particle size analysis, %buoyancy, drug entrapment efficiency, % yield and in vitro drug release. All the results were found to be in acceptable limit. The optimized formulation were subjected to different release kinetic model like zero order, First order, Higuchi, korsemeyer peppas and Hixon-crowell. The korsemeyer peppas model was accepted due to its highest value of slop (n) (0.9890). The optimized formulation again subjected to stability studies as per the ICH Guideline. The formulation was found to be stable under the provided condition of temperature and humidity.