Objective To evaluate the therapeutic effects and mechanism of azithromycin treatment in bleomycin induced pulmonary fibrosis of rats. Methods Animal model of bleomycin A5 induced pulmonary fibrosis was established in rats.36 animal models were divided into two groups: a bleomycin induced pulmonary fibrosis group and a azithromycin group in which the animal models were treated with azithromycin (80 mg/kg once a day for three continuous days in a week). The animals of the two groups were killed at the first,second and fourth week respectively.Another six rats constituted a normal control group, instillated withsaline intratracheally and killed at the first week. Pathological changes activity of nuclear factor κB (NF κB) of alveolar macrophage, cytokine tumor necrosis factor (TNF)α、transforming growth factor β (TGF β)mRNA expression and protein levels of alveolar macrophage and lung tissue were studied or measured. Results Amelioration of alveolitis and lung fibrosis after treatment with azithromycin was shown in pathological section( P 0.05). The activity of NF κB was significantly higher in one week pulmonary fibrosis model than that in normal control and its level in alveolar macrophage reduced (67.2%) after treatment with azithromycin. The level of protein and mRNA of TNFα、TGF β in lung tissue and alveolar macrophage was increased in the early stage of pulmonary fibrosis and reduced after treatment with azithromycin( P 0.05). Conclusion It is suggested that azithromycin might be a therapeutic drug for pulmonary fibrosis in the future. Azithromycin reduced the degree of alveolitis and fibrosis through inhibition of the activity of NF κB and the expression of TNFα、TGF β mRNA and lowering the level of protein in alveolar macrophage and lung tissue in the early stage of pulmonary fibrosis . This might be one of the mechanisms of azithromycin treatment in pulmonary fibrosis.