Idiopathic pulmonary fibrosis (IPF) is a lethal idiopathic interstitial pulmonary disease characterized by progressive deterioration in lung function that commonly affects eldly people. The pathogenesis of the disease is incompletely understood and therefore lacking effective therapy. Ouabain a digitalis has been reported to be able to suppress lung fibroblast activation via downregulatingTGF-beta-smad signal pathway in vitro. Here, we investigated the effects of ouabain in pulmonary fibrosis in vivo. Pulmonary fibrosis was induced in C57/BL6 mice by a intratracheal instillation of bleomycin (2.0 mg/kg), ouabain (0.6 mg/kg) was given daily via intraperitoneal injection for one week starting at 7 days after intratracheal instillation of bleomycin. Our study showed ouabain significantly reduce alpha-SMA, fibronectin and collagen I expression in lung fibrosis animal model. Further, ouabain inhibits cells proliferation and promotes apoptosis of lung fibroblasts in vitro. In conclusion, our results indicate ouabain a novel effective drug that inhibits lung fibrosis progression.