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目的 Pulmonary fibrosis is a progressive disease with poor prognosis and treatment.It is characterized by lung fibroblast actvation and extracellular matrix(ECM) deposition,.Heat shock protein 90(Hsp90) plays a significant role in multiple cellular process, especially extracellular heat shock protein 90 alpha(eHsp90α) can promotes wound healing induced by fibroblast actvation and migration.方法 Recombinant TGF-β1 was used to induce human lung fibroblast activation and ECM synthesis.The protein level of intracellular Hsp90α and Hsp90β was detected by western blot.The condition media of lung fibroblast was collected to detected the expression of extracellular Hsp90α and Hsp90β.Anti-Hsp90 monoclonal antibody (mAb) was applied at 50ug/ml.Lung fibroblast activation and ECM production were respectively evaluated by expression of alpha smooth muscle actin(α-SMA), fibronectin and collagen Ⅰ.C57/BL mice modle of pulmonary fibrosis was induced by 3U/kg bleomycin (BLM).eHsp90α in BALF was determined by Elisa.Pulmonary fibrosis was assesssed by HE staining, masson-trichrome staining, the content of hydroproline.Futhermore, the expression of Hsp90α, α-SMA, collagen Ⅰ was determined by immunohistochemistry.结果 Secretion of Hsp90α and Hsp90β by human lung fibroblast , as well as the expression of intracellular Hsp90α and Hsp90β, is significantly increased after stimulation by TGF-β1 .Anti-Hsp90α mAb prevents lung fibroblast activation and ECM synthesis, shown by decreased expression of α-SMA, fibronectin and collagen Ⅰ.Moreover, eHsp90α is greatly upregulated in BALF of BLMinduced fibrotic mice.Hsp90α is increased in BLM-induced fibrobtic lung.Anti-Hsp90α mAb can alleviate pulmonary fibrosis induced by BLM indicated by decreased ECM deposition and downregulated expression of α-SMA,collagen Ⅰ.结论 eHsp90α promotes lung fibroblast activation and ECM production, therefore plays an important role in the development of pulmonary fibrosis.Anti-Hsp90α monoclonal antibody significantly ameliorate pulmonary fibrosis induced by BLM with suppressing lung fibroblast activation and ECM deposition.Our results presents a potential and safer therapeutic target for pulmonary fibrosis.