Bleomycin causes pulmonary fibrosis by increasing free oxygen radicals. Cigarette smoke is a strong oxidant which adversely affects pulmonary tissue. We evaluated the effects of cigarette smoke administered with intratracheal bleomycin on pulmonary tissue. We studied 3 groups of rats (n=10): one group received intratracheal saline and served as a control; one received intratracheal Neomycin (IT) (0.5 U/100 g body weight, single dose on the first day), and one group received intratracheal bleomycin (single dose on first day) and tobacco smoke (two times per day) (IT-S). After 4 weeks, the levels of malondialdehyde (MDA) and nitric oxide (NO) and the activities of superoxide dismutase (SOD) and xanthine oxidase (XO) were assayed in the homogenate of the lung tissue samples. The severity of interstitial fibrosis was assessed using the grading system described by Ashcroft. There was more intensive fibrosis in the IT and IT-S than in the control samples (P<0.001). The levels of MDA., NO and activity of XO were significantly increased (P<0.001, <0.002 and <0.002, respectively), and SOD activity (P<0.001) was significantly decreased in the IT group when compared to these values in the control group. The concentration of NO was significantly decreased (P<0.002), and SOD activity was significantly increased (P<0.05) in the lung tissue samples of the IT-S group. Theoretically, the combination of cigarette smoke and bleomycin may have a synergistic effect on oxidative lung injury. In conclusion, we showed that inhalation of cigarette smoke provides protection against oxidative stress in the lung tissue of rats with bleomycin-induced pulmonary fibrosis.