It is well known that maintenance therapy using Chai-hu-gui-zhi-tang (CHGZT), a traditional Chinese medicine, has been proven to prevent the recurrence of peptic ulcers. However, little is known as to whether or not it has protective effects against acute gastric injury. In the present study, we investigated the preventive effects of pretreatment with CHGZT extract on the development of water immersion restraint stress-induced acute gastric ulceration in male Wistar rats. The CHGZT extract (50, 250, 500 mg/kg b.w., p.o.) was given to rats before they were exposed to 2 or 4 hr of water immersion restraint stress; they were then were sacrificed immediately after stress exposure. Gastric mucosal lesions were evaluated macroscopically, and the gastric mucosal and hepatic non-protein sulfhydryls (NP-SH) were measured simultaneously. The results indicate that exposure to water immersion restraint stress resulted in the development of acute gastric stress erosions. Pretreatment with CHGZT extract caused a significant reduction of stress lesions and an increase in the gastric mucosal NP-SH and hepatic NP-SH concentrations. We conclude that the anti-ulcer response and extensive antioxidant effect of Chai-hu-gui-zhi-tang may be valuable in prevention of experimental gastric mucosal lesions in rats because it possesses preventive and gastroprotective effects.