Aging has been proposed as the major risk factor in most neurodegenerative disorders. Oxidative stress is one of the widely accepted hypotheses to explain the pathogenesis of the senescence-related disorders. in this research report we aimed to study the changes in the levels of malondialdehyde as an indicator of lipid peroxidation and glutathione (GSH) of anti-oxidant status during aging. We also studied the effects of exogenous melatonin (MLT) on lipid peroxidation and glutathione levels of different brain regions. A total of forty-seven, 4 (young), 14 (middle-aged) and 20 (aged) months-old male Wistar-albino rats were used in the study. The MDA levels were significantly correlated with increased age (P<0.001). The MDA levels were similar in the different regions of the brain in the younger rats. However, the MDA levels of the cerebellum were significantly lower than that of the frontal and occipital cortex of the aged animals. Exogenous melatonin treatment significantly decreased the MDA levels of all the examined brain regions in the aged groups (p<0.001). The GSH levels of all the examined brain regions were similar in young and middle-aged rats. The GSH levels were inversely correlated with the increasing age. While exogenous melatonin did not have any significant effect on the CSH levels of the different brain regions in the younger rats, it significantly increased in the aged group. Exogenous melatonin can prevent the increased production of age-related lipid peroxidation products and might have a potential role for retardation of age-related oxidative events. (C) 2008 Elsevier B.V. All rights reserved.