ABSTRACT. 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.KEY WORDS: antioxidant effect, Chai-hu-gui-zhi-tang (CHGZT), gastric ulcer, non-protein sulfhydryls, water immersion restraint stress.J. Vet. Med. Sci. 72(6): 679-685, 2010 Chai-hu-gui-zhi-tang (CHGZT), a traditional Chinese herbal prescription, is a mixture of nine herbs, Bupleuri radix, Scutellariae radix, Ginseng radix, Cinnamomi ramulus, Paeoniae radix, Zingiberis rhizome, Pinelliae tuber, Glycyrrhizae radix and Zizyphi fructus, has shown a good antioxidant effect and has been used to prevent the formation of nervous lesions, such as epilepsy, Alzheimer's disease and developmental defects of neurons during pregnancy and after birth [12,25]. In traditional Chinese medicine, CHGZT has been used in therapies for gastric ulcers and gastritis, but the underlying mechanisms are not well understood. Among the herbal drugs contained in GHGZT, Scutellariae radix [6] and Panax ginseng [11] have been used extensively, and their clinical efficacies have been documented in regard to anti-ulcer activity. The flavonoids of Scutellariae radix have been found to be free radical scavengers [3]; free radicals play an important role in ulcerative and erosive lesions of the gastrointestinal tract. Glycyrrhizae radix water extract and its two major constituents, glycyrrhizin and 3-glycyrrhetinic monodesmoside, may be promising for amelioration of hypoxia (ischemia)-reoxygenation (reperfusion) injury and improvement of renal function by acting as antioxidant and oxygen radicalscavenging agents [32].It is well known that stress plays a major role as a risk factor in the occurrence of stomach erosion and ulcers [22].Water immersion restraint stress (WIRS) mimics the clinical a...