Alpha-tocopherol is an antioxidant which has been suggested to have anti-inflammatory and analgesic activities in humans. However, the anti-inflamatory and analgesic effetcs of alpha-tocopherol in mice had not been studied. Therefore, this study was designed to determine the antinociceptive doses of alpha-tocopherol in mice. In addition, this study aims to compare the activity of alpha-tocopherol with those of dipyrone and aspirin and to investigate the role of nitric oxide (NO) in the antinociceptive activity of alpha-tocopherol in mice. Hot plate, tail clip and tail flick tests were applied to evaluate the central antinociceptive activity using 1, 5, 25 and 100 mg/kg intraperitoneal doses of alpha-tocopherol. A dose-dependent antinociceptive activity was observed at low doses, the most effective dose was 25 mg/kg. Furthermore, it was observed that co-administration of L-arginine (100 mg/kg) with alpha-tocopherol (25 mg/kg) reduced the antinociceptive activity and this activity was compared with those of dipyrone and aspirin. These results showed that alpha-tocopherol has central antinociceptive activity and that NO may play a role on its effect. © 2006 VSP.