Protective effect of quercetin and alpha-tocopherol on experimental reflux oesophagitis in rats was investigated. Rats received quercetin, (100 mg/kg), alpha-tocopherol (16 mg/kg), omeprazole (30 mg/kg) given at 1 h prior to surgery. Quercetin and alpha-tocopherol significantly inhibited the oesophagitis index to 1.33+/-0.12 (P<0.001) and 1.83+/-0.14 (P<0.001) respectively, as compare to control group 3.5+/-0.21. Further, acid and pepsin out put of gastric contents were significantly decreased in treated groups. Indeed, quercetin significantly inhibited the lipid peroxidation (from 0.69+/-0.05 to 0.43+/-0.04 nmol of malonyldialdehyde (MDA)/mg protein) (P<0.001) and increased in levels of catalase to 29.5+/-2.7 units of catalase activity/mg protein and superoxide dismutase (SOD) to 92.4+/-10.5 units/mg protein (P<0.001). The alpha-tocopherol and omperazole showed significant inhibition in lipid peroxidation (0.34+/-0.02 and 0.38+/-0.01) (P<0.01) and enhanced the activities of catalase (34.3+/-3.6 and 31.5+/-3.4) (P<0.01) and SOD (87.3+/-9.2 and 76.60+/-6.9) activity. Quercetin and alpha-tocopherol treated group significantly increased the glutathione level to 36.5+/-2.78 (P<0.01) and 32.1+/-2.34 (P<0.05) respectively. However, it altered the elevated levels of sialic acid and hexose contents in oesophageal tissue. Indeed, quercetin significantly decreased the elevated plasma histamine content (P<0.05). Quercetin and alpha-tocopherol significantly attenuated the elevated level of collagen in oesophageal tissue as of the omeprazole. The results suggest that antioxidants could attenuate the severity of reflux oesophagitis and prevent the oesophageal mucosal damage and validate its therapeutic use in gastroesophageal reflux disease.