The objective of present research work was to develop floating microspheres for oral delivery of clarithromycin for treatment of Helicobactor pylori to provide prolonged contact time of to the stomach. Floating microsphere were prepared by solvent diffusion and evaporation method and characterized for particle size, % entrapment efficiency, % buoyancy and surface morphology by using scanning electron microscopy (SEM). Prepared formulation has particle size 142.26 nm, entrapment efficiency 79.22% and buoyancy 93.35%. In vitro drug release study and in vivo radioimaging study also carried out. The buoyancy and release profile of the floating microspheres shown have potential for delivery of clarithromycin to the stomach. These microspheres resided in the stomach upto 6 hour for treatment of H. pylori.