Nonsteroidal anti-inflammatory drugs such as indomethacin induce severe gastric mucosal damage in humans and rodents. In the present study, the in vivo protective effect of astaxanthin on indomethacin-induced gastric lesions in rats was investigated. The test groups were injected with indomethacin (25 mg/kg) after the oral administration of astaxanthin (25 mg/kg) for 1, 2, and 3 days, while the control group was treated only with indomethacin. Thiobarbituric acid reactive substances in the gastric mucosa, as an index of lipid peroxidation, increased significantly after indomethacin administration and this increase was inhibited by oral administration of astaxanthin. In addition, pretreatment with astaxanthin resulted in a significant increase of the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px). Histologic examination clearly revealed acute gastric mucosal lesions induced by indomethacin in the stomach of the control group, but were not observed in that of the test group. These results indicate that astaxanthin activates SOD, catalase, and GSH-px, and removes the lipid peroxides and free radicals induced by indomethacin. It is evident that astaxanthin acts as a free radical quencher and antioxidant, and is an effective molecule in the remedy of gastric mucosal lesions.