This study is designed to observe the effects of N-acetylcysteine (NAC) on doxorubucine-induced cardiac toxicity in rats both histologically and biochemically. Totally 32 rats divided equally into four groups were studied. The first group received only 200 mg/kg NAC intraperitoneal (i.p.) once every 24 h for 5 days (group 1); the second group received 20 mg/kg doxorubucine (DOX) i.p. single dose plus NAC 200 mg/kg i.p. once every 24 h for 5 days (group 2); the third group received DOX 20 mg/kg DOX i.p. single dose (group 3) and the fourth group, which is also the control group, received saline (group 4). Following 24 h of the final dose, blood samples were drawn from a portal vein and heart tissue were obtained. Tissue thiobarbituric acid reactive substance (TBARS) and nitric oxide (NO) levels were highest in the DOX group. In the DOX-treated rats, serum TBARS, NO, aspartate transaminase, lactate dehydrogenase and creatine kinase levels were highest when compared with other groups. Except for serum superoxide dismutase levels, all other parameters differed significantly between the DOX plus NAC group and the DOX group. In the DOX plus NAC group, general architecture was preserved better than the DOX group and myofibril loss was minimal compared with the DOX group. NAC demonstrated, both biochemically and histologically, to be effective in the prevention of DOX-induced cardiotoxicity in rat models. Evaluation of NAC's effect on DOX toxicity warrants further clinical trials on cancer patients.