Previous reports suggested that cigarette smoke had a protective effect of on the development of hypersensitivity pneumonitis (HP). However, smoking rate in chronic pigeon breeder's lung (PBL) seemed to be high in our clinical experiences. We developed a murine model of PBL by intranasal instillation with pigeon dropping extracts (PDE) for 4 weeks (short-term exposure) and 17 weeks (long-term exposure) to investigate the effect of cigarette smoke on disease processes. In this model, lung inflammation associated with the production of anti-PDE antibodies and antigen dependent lymphocyte proliferation was induced. Long-term exposure to PDE without cigarette smoking resulted in an increase in lung weight/body weight ratio, total cell number in bronchoalveolar lavage (BAL) fluid, and content of hydroxyproline in the lung compared to shortterm exposure. After a short-term exposure, cigarette smoke lessened the lymphocytosis in BAL fluid, and lymphocyte proliferation. On the other hand, after a long-term exposure cigarette smoke increased lung hydroxyproline. These results suggest that a short-term cigarette smoking attenuates lung inflammation, but a long-term cigarette smoking enhances lung inflammation with fibrosis.