The aim of this study was to investigate the effects of chronic, daily, 30-d administration of manganese chloride (MnCl2) to male Sprague-Dawley rats on lipid peroxidation and changes of trace elements (manganese, iron, copper, zinc) in various brain regions. Rats were intraperitoneally injected with MnCl2 (20 mg/kg) once daily for 30 consecutive days. The Mn accumulated in frontal cortex, corpus callosum, hippocampus, striatum, hypothalamus, medulla, cerebellum, and spinal cord. Malondialdehyde, an end product of lipid peroxidation, was markedly decreased in frontal cortex and cerebellum. An increased level of Cu was observed in frontal cortex, medulla, and a cerebellum. A decreased Fe level was found only in cerebellum, and a decreased Zn level was observed in hippocampus and striatum. In a second group of animals, Mn (20 mg/kg/d) and glutathione (GSH, 15 mg/kg/d) were administered ip for 30 d. In CSH-Mn-treated rats, compared to Mn-treated rats, MDA concentrations were significantly reduced in frontal cortex, medulla and cerebellum. The changes of trace elements in rat brain were similar to the Mn-treated group. We suggest that Mn is an atypical antioxidant, as well as not involved in oxidative damage in rat brain. Fe and Cu may play roles in the protective effect of Mn against lipid peroxidation in rat brain.