ObjectiveTo investigate the role of PI3K/Akt/HIF-1αsignaling pathway in bleomycin-induced pulmonary fibrosis in mice. MethodsFifty-six C57BL/6 mice were randomly divided into a control group and a bleomycin (BLM) group.The pulmonary fibrosis model was induced by single intratracheal instillation of BLM(2.5 mg/kg) in the BLM group.Similarly, 0.9% saline was instilled directly into the trachea in the control group.Then all mice were sacrificed on 21st day.The lungs were collected for morphometric analysis with HE and Masson staining.The degree of pulmonary fibrosis was evaluated with Ashcroft score and content of hydroxyproline.The activity of PI3K/Akt/HIF-1αsignaling pathway and pro-surfactant protein C (Pro-SPC) were measured by Western blot.The level of collagen3 mRNA was assessed with quantitative real time PCR analysis.Collagen3 protein and numbers of apoptosis cells were observed with immuno-histochemistry. ResultsIt was exhibited that the thickening alveolar septa, accumulation of inflammatory cells, and fibrous obliteration in the BLM group but not in the control group.There was a significant difference in Ashcroft score and hydryoproline content in the BLM group.Meanwhile, the activity of PI3K/Akt/HIF-1αsignaling pathway was up-regulated and the protein of Pro-SPC was decreased in the BLM group.It was revealed that the numbers of apoptosis cells, expressions of Collagen3 protein and mRNA were increased in the BLM group. ConclusionAberrant activity of PI3K/Akt/HIF-1αsignaling pathway may aggravate the pulmonary fibrogenesis.