Frequently used for humans as a nonsteroidal anti-inflammatory drug, naproxen has been known to induce ulcerative gastric lesions. The present study was undertaken to investigate the in vivo therapeutic effect of astaxanthin, isolated from a Xanthophyllomyces dendrorhous mutant, against naproxen-induced gastric antral ulceration in rats. The rats were treated with three doses of astaxanthin [1, 5, and 25 mg/kg body weight (B.W.), respectively] once daily for 2 weeks after pretreatment of 80 mg of naproxen/kg B.W. twice daily for 3 days, while the control rats received only 80 mg of naproxen/kg B.W. twice daily for 3 days. The oral administration of astaxanthin (1,5, and 25 mg/kg B.W.) showed a curative effect against naproxen (80 mg/kg B.W.)-induced gastric antral ulcer and reduced the elevated lipid peroxide level in gastric mucosa. In addition, astaxanthin treatment resulted in significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly proved that acute gastric mucosal lesion induced by naproxen nearly disappeared after the astaxanthin treatment. These results suggest that astaxanthin eliminated the lipid peroxides and free radicals induced by naproxen and may be a potential candidate for remedy of gastric ulceration.