Reactive oxygen species (ROS) have been implicated in the etiology of indomethacin-induced gastric mucosal damage. This study investigated amiodarone’s protective effects against oxidative gastric mucosal damage induced by indomethacin. Amiodarone is a widely used antiarrhythmic agent. We have investigated alterations in the glutathione level, and the activities of antioxidative enzymes [superoxide dismutase, catalase, glutathione s-transferase glutathione reductase and myeloperoxidase], as markers for ulceration process following oral administration of amiodarone and ranitidine in rats with indomethacin-induced ulcers. In the present study we found that 1) amiodarone, lansoprazole and ranitidine reduced the development of indomethacin-induced gastric damages, at a greater magnitude for amiodarone and lansoprazole than for ranitidine; 2) amiodarone and ranitidine alleviated increases in the activities of catalase and glutathione s-transferase enzymes resulting from ulcers; 3) amiodarone and ranitidine ameliorated depressions in the glutathione level and the activities of superoxide dismutase and glutathione reductase enzymes caused by indomethacin administration; and 4) all doses of amiodarone amplified the myeloperoxidase activity resulting from indomethacin-induced gastric ulcers. The results indicate that the gastroprotective activity of amiodarone, which may be linked to its intrinsic antioxidant properties, cannot be attributed to its effect on myeloperoxidase activity.