ObjectiveTo explore the effect of cigarette smoke exposure on the expression of 4-hydroxynonenal (4-HNE) and gamma-glutamylcysteine synthetase(γ-GCS)in bronchoalveolar lavage fluid (BALF) and peripheral blood of rats. Methods Thirty male Wistar rats were randomly divided into three groups:non-smoking group, 6-weeks smoking group and 12-weeks smoking group. 4-HNE and γ-GCS in BALF and peripheral blood were quantitatively analyzed by avidin-biotin complex enzyme-linked immunosorbent assay (ABC-ELISA). Results(1)The expressions of 4-HNE in BALF and peripheral blood of rats in the 6-weeks smoking group(21.376±2.80; 18.333±2.585)and the 12-weeks smoking group(28.634±2.999；22.754±3.882)were significantly higher than those in the non-smoking group(15.917±1.584；12.305±1.822)(all P<0.01), and those of the 12-weeks smoking group were significantly higher than those of the 6-weeks smoking group (all P<0.01).(2)The expression of γ-GCS in BALF and peripheral blood of rats in the 6-weeks smoking group(15.802±1.646; 16.221±1.577)were significantly higher than those in the non-smoking group(13.525±2.311；11.847±1.171)(P<0.05； P<0.01), and those of the 12-weeks smoking group(11.527±1.606；9.015±1.569)were significantly lower than those of the non-smoking group (P<0.05；P<0.01).(3)The level of 4-HNE in BALF and peripheral blood in the 6-weeks smoking group was positively related with that of γ-GCS (r=0.764,r=0.674), and the level of 4-HNE in BALF of the 12-weeks smoking group was negatively related with γ-GCS(r=-0.777)(all P<0.05), but there was no significant correlation between the 4-HNE and γ-GCS in peripheral blood of the 12-weeks smoking group. Conclusions Cigarette smoke exposure can upregulate the expression of 4-HNE and γ-GCS in BALF and peripheral blood in rats. As smoking is prolonged, the expression of γ-GCS is gradually reduced, which indicates that 4-HNE and γ-GCS may play an important role in the oxidation/antioxidant imbalance in chronic obstructive pulmonary disease.