Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. Inflammation and apoptosis have been suggested to be important mechanisms for COPD. IL-17 superfamily has been associated with chronic inflammation and diminished responses to steroids. It is reasonable to consider that IL-17 may play a role in the pathogenesis of COPD. In this study, we examined IL-17 expression in mice exposed to cigarette smoke (CS), and investigated the contribution of IL-17 to CS-induced inflammation and alveolar cell apoptosis in IL-17^-/- mice. After exposing wild-type and IL-17^-/- mice to main-stream CS for 4 weeks, IL-17A, but not IL-17F, expression was increased in mice upon CS exposure. Neutrophil infiltration in the lung of IL-17^-/- mice was significantly decreased. In IL-17^-/- mice, there is reduced expression of IL-6, MIP-2 and MMP12 compared to wild-type mice after CS exposure. The number of apoptotic type II alveolar cells was significantly increased in CS-exposed wild-type mice but not in IL-17^-/- mice. The effect of IL-17A on type II alveolar cell apoptosis was confirmed in vitro through either addition of IL-17A or transient knockdown of IL-17A by siRNA transfection in type II alveolar cells. These findings suggest that IL-17A plays an important role in the inflammatory response to CS exposure through increased multiple inflammatory mediators. Moreover, IL-17 may also contribute to type II alveolar cell apoptosis. This study opens a new option in targeting IL-17A to modulate inflammatory response to CS and may be the bases for new therapy for COPD.