Previous studies have indicated a pivotal role of reactive oxygen species in the pathomechanism of gastric ulcer. Recent studies demonstrated that thymoquinone (TQ) had an antioxidant effect on injuries caused by various toxic agents in different experimental models. The present study was planned to test whether TQ, the main constituent of the volatile oil of Nigella sativa seeds, was capable to exert beneficial effects on acute gastric ulcer model in rats. We examined antiulcerative and antioxidant effects of TQ on ethanol (EtOH)-induced gastric lesions in rats. The data we collected showed that gastric ulcer caused by absolute EtOH induction resulted in an increase in lipid peroxidation, represented by malondialdehyde level as well as by superoxide dismutase level, an antioxidant enzyme, whereas it resulted in a decrease in glutathione content in rat stomach tissue. Thymoquinone (20 mg/kg) administration reduced the ulcer index and the malondialdehyde level, and reversed the glutathione depletion. However, it did not statistically change the high superoxide dismutase activity induced by EtOH. These results suggest that TQ could inhibit the development of EtOH-induced gastric ulcer, and gastroprotective action of TQ might be in part dependent on its antioxidant property. (c) 2005 Elsevier Inc. All rights reserved.