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The aim of the study was to develop microspheres containing Amoxicillin trihydrate and Metronidazole for the treatment of gastric ulcer using chitosan as mucoadhesive polymer. Microspheres were prepared by cross linking it with sodium tripolyphosphate. The influence of formulation parameters were studied on particle size, content uniformity, swelling studies and mucoadhesive studies. In vitro release of chitosan microspheres were studied in 0.1 N HCl at 37 0±0.5 0 C. The prepared microspheres were characterized by DSC. The morphology of microspheres was investigated by scanning electron microscopy (SEM). It was found that chitosan microspheres showed mucoadhesive property and the sustained drug release over a period of 10 hours. SEM photograph confirmed the spherical shape of microspheres. It was observed from the DSC that the decomposition temperatures of pure drugs and formulations remained the same indicating there is no interaction between the drugs and polymers used. It can be concluded that the prepared mucoadhesive microspheres can be used as carriers for the treatment of gastric ulcer caused by H. Pylori since they increase the residence time of the drugs inside stomach and give better therapeutic action.