Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are widely used in the treatment of inflammation, fever and pain. However, NSAIDs cause gastric damage as a major adverse reaction. In this study, the effects of vegetable oils (corn, olive and sunflower oils) and alpha-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin were evaluated in rats. Results showed that indomethacin given with sunflower, corn and olive oils reduced paw edema induced by carrageenan by 79.5%, 74.0% and 60.5%, whereas individual indomethacin and diclofenac reduced paw edema by 56.2% and 50.7%, respectively. Furthermore, it has been found that the vegetable oils possess significant anti-inflammatory effect against paw edema when given alone. These results showed that the vegetable oils have beneficial effects on reduction paw edema induced by carrageenan. Besides, the administration of indomethacin together with the vegetable oils and et-tocopherol did not cause a statistically significant gastric damage in rats (P > 0.05). However, indomethacin caused statistically significant gastric lesions as compared with untreated rats (P < 0.05). Moreover, it was also found that the effects of the vegetable oils and alpha-tocopherol improved the levels of antioxidant defense systems in rat stomach tissues against oxidative damage. These results suggest that indomethacin as well as other NSAIDs do not have any adverse effect on the gastrointestinal tract when they are used together with vegetable oils and vitamin E or as the preparations of the oils. (C) 2008 Elsevier B.V. All rights reserved.