Abstract: OBJECTIVE To study the protective effect of Ento-A extract from Periplaneta americana on gastric mucosa of acute gastritis and to explore its mechanism. METHODS Rats were divided into normal control group, model control group, Kangfuxin liquid group, cimetidine group, Ento-A high and low dose group. After 8 days of continuous administration, the model of gastric mucosal injury was established by intragastric administration with 20 mg·mL^-1 sodium salicylate solution and 80% ethanol. The protective effect of Ento-A extract on the gastric mucosa was evaluated by gastritis scoring and histopathological scoring. The expression levels of MDA, TNF-α, SOD, IL-1β in serum and epidermal growth factor(EGF) in gastric tissue homogenate of rats were detected by ELISA to investigate the protective mechanism of Ento-A on gastric mucosa. RESULTS Compared with the model control group, Kangfuxin liquid, cimetidine and Ento-A could significantly reduce the expression of TNF-α, MDA, IL-1β, and increase the level of SOD in the serum of rats with acute gastritis(P<0.05, P<0.01), increase the expression of EGF in the gastric homogenate of rats with acute gastritis(P<0.05, P<0.01). CONCLUSION Ento-A has obvious protective effect on gastric mucosal injury, and its mechanism may be related to reducing the secretion of inflammatory factors, resisting free radical damage and promoting tissue repair.