Impairment of thyroid functions brings about pathological changes in different organs of body. Findings of in vivo and in vitro studies indicate that thyroid hormones have a considerable impact on oxidative stress. Melatonin reduces oxidative damage through its free radical eliminating and direct anti-oxidant effects. The present study was undertaken to determine how a 3-week period of intraperitoneal melatonin administration affected oxidative damage caused in experimental hyperthyroidism in rat. The experimental animals were divided into 3 groups (control, hyperthyroidism, hyperthyroidism + melatonin). Malondialdehyde (MDA) and glutathione (GSH) levels were determined in different tissues. MDA levels in cerebral, liver and cardiac tissues in hyperthyroidism group were significantly higher than those in control and hyperthyroidism + melatonin supplemented groups (p < 0.001). The highest GSH levels were observed in the group that was administered melatonin in addition to having hyperthyroidism (p < 0.001). These results show that hyperthyroidism increased oxidative damage in cerebral, hepatic and cardiac tissues of rat. Melatonin supplementation may also suppress oxidative damage. © 2006 Elsevier Inc. All rights reserved.