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Background: Iron is essential metal for living. We reported association of serum iron and pulmonary function in smoking man. Further, several studies show hypoironemia and anemia were associated with pulmonary function or respiratory disease. However, it is not clear how iron play role in lungs. We used cigarette smoke exposure model to evaluate influence of iron deficiency. Methods: Iron deficient (ID) or normal diet (control) were fed to C57BL/6J male mice for 3 weeks. Later, mice were exposed cigarette smoke. Bronchoalveolar lavage (BAL) and pulmonary function tests were performed after 2 weeks of cigarette exposure or 8 weeks of cigarette exposure. Results: In mice exposed to CS for 2 weeks, concentration of alveolar macrophages in BAL fluid recovered from ID mice were significantly increased compared to those from control mice. Further, interleukin (IL)-6 levels in BAL fluid were significantly increased from baseline in ID mice, but this increase of IL-6 was not observed in control mice. In mice exposed to CS for 8 weeks, total lung capacity in ID mice was significantly larger than those in control mice. Conclusion: Iron deficiency may enhance airway inflammation and worsen pulmonary function in mice exposed to cigarette smoke.