We aimed to evaluate the effects of smoking on the histopathology and the oxidant-antioxidant status of lungs and to test the effects of N-acetylcysteine (NAC) on the induced changes. Rabbits were exposed to cigarette smoke (CS) in a glass chamber for one hour daily for one month. An NAC control group was given intraperitoneal NAC only. CS + NAC rats were exposed to smoke and given intraperitoneal NAC. A control group was exposed to clean air only. At the end of one month, animals were sacrificed and lung tissues were examined histopathologically. Blood levels of protein sulfhydryls, carbonyls, prostaglandin F(2alpha) (PGF(2alpha)) and malondialdehyde (MDA) were measured. Intraparenchymal vascular congestion and thrombosis, intraparenchymal hemorrhage, respiratory epithelial proliferation, number of macrophages in the alveolar and bronchial lumen, alveolar destruction, emphysematous changes and bronchoalveolar hemorrhage scores were significantly increased in rabbits exposed to CS compared with the control group. Protein sulfhydryls were significantly decreased; carbonyls, PGF(2alpha) and MDA levels were significantly increased in the smoke exposed rabbits. Administration of NAC to rabbits exposed to CS caused a reduction in the bronchoalveolar hemorrhage score and blood PGF(2alpha) levels. Other parameters were unaffected by NAC. Exposure to CS causes severe histopathological changes and negatively effects the oxidant-antioxidant status in the lungs of rabbits. A low daily dose of NAC has some ameliorative effects on histopathological changes and oxidant-antioxidant status of the lungs in smoke exposed rabbits.