The effect of a proton pump inhibitor, omeprazole (OPZ), in combination with mouse epidermal growth factor (EGF), on the healing of chronic gastric ulcers induced by acetic acid in submandibular glands removed rats (SMR rat) was investigated. Four separate groups of SMR rats were orally administered 1 ml of distilled water (control), 100 mg/kg of OPZ alone (OPZ), 5 micrograms/kg of mouse EGF alone (EGF), or combination with (EGF + OPZ) twice daily. Two weeks later, ulcer areas of four groups were measured and expressed as the ulcer index (UI). The UI of the OPZ and EGF + OPZ group was significantly reduced as compared with that of the control. Furthermore, the UI of the EGF + OPZ group was significantly smaller than that of the EGF group. The present study indicates that the proton pump inhibitor promotes healing of chronic gastric ulcers in SMR rats and the effect of the proton pump inhibitor is enhanced by administration of mouse EGF.