Chronic ethanol administration is able to induce an oxidative stress in the central nervous system. N-Acetylcysteine (NAC) has antioxidant properties; as a sulphydryl donor, it contributes to the regeneration of glutathione and it acts through a direct reaction with hydroxyl radicals. In this study we investigated a possible beneficial effect of NAC on some of the free radical related parameters. Twenty four male Wistar rats were divided in to three groups and were given ethanol (Group 1), ethanol and NAC (Group 2) and isocaloric dextrose (Group 3). Ethanol and NAC were given intragastrically at doses of 6 g/kg/day and 1 g/kg/day, respectively. Our results show that chronic ethanol intake elicits statistically significant increase in MDA and NO levels and decrease in SOD and GSH levels in both plasma and brain (p < 0.001). GPx levels decreased in erythrocytes (p < 0.001). CAT activity showed significant decrease only in brain samples (p < 0.001). NAC administration effectively restores the above results to nearly normal levels. Therefore we suggest that reactive free radicals are, at least partly, involved in the ethanol-induced injury of brain cells and NAC mitigate the toxic effects of ethanol on the oxidant-antioxidant system of rat plasma and brain.