Abstract: AIM: The protection and anti-oxidative mechanism of 2(3)-tert-butyl-4-hydroxyanisole(BHA) against ethanol-induced gastric mucosa lesion in rats were evaluated. METHODS: Gastric mucosal lesions were induced by oral administration of absolute ethanol in rats. The activities of some enzymes and MDA content in gastric mucosa were determined. RESULTS: Oral administration of BHA at 100 mg.kg^-1 and 20 mg.kg^-1 reduced significantly the gastric lesion induced by ethanol, and inhibited the increase of MDA in gastric mucosa. Compared with normal control, BHA was found to increase the activities of quinone reductase (QR) and glutathione reductase (GR). In ethanol-treated rats decreases of QR, GR and SOD were observed. However, BHA was shown to prevent the decrease of QR, GR and SOD in gastric mucosa induced by ethanol. CONCLUSION: These results suggest that BHA has protective effect against ethanol-induced gastric mucosal lesion via increasing the activities of anti-oxidative enzymes and anti-lipid peroxidation.