Fructus Evodiae is a widely used herbal medicine with anti-inflammatory and analgetic activities in China. The present study was designed to investigate the effect of Fructus Evodiae water extract (FE) on ethanol-induced gastric lesions in rats. Three hours before ethanol challenge, animals were intraperitoneally treated with FE (424.8 mg/kg, 141.6 mg/kg, and 47.6 mg/kg). Subsequently, we employed ex-vivo chamber technique to examine the effect of FE on gastric transmucosal potential difference (PD) changes. NO(x) (nitrate and nitrite) in gastric perfusate and gastric lesion index of whole glandular stomach were determined by intubation. The results showed that FE dose-dependently accelerated the recovery of PD reduction by ethanol, and increased NO(x) production in gastric perfusate. FE also inhibited gastric lesion formation in a dose-dependent manner. These results suggested that FE prevented ethanol-induced gastric mucosal lesions by strengthening the mucosal barrier integrity and increasing gastric mucosal nitric oxide (NO) synthesis.