ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis is an irreversible lung disease with a high mortality rate. Zhebeimu (ZBM, Fritillaria thunbergii Miq.) is a Chinese medicine commonly used for the treatment of pulmonary fibrosis in China. AIM OF THE STUDY: In this study, the protective effect and mechanism of ZBM extract in the treatment of pulmonary fibrosis were investigated in vivo and in vitro. MATERIALS AND METHODS: The protective effect of ZBM extract was assessed using an in vivo model of bleomycin (BLM) tracheal drip and transforming growth factor-β(TGF-β1)-induced fibroblasts to simulate pulmonary fibrosis, and lung function, lung histopathological status and hydroxyproline were tested. Relevant pathways were detected using protein blotting, immunofluorescence and immunohistochemistry. RESULTS: ZBM extract effectively improved lung function, inflammatory changes and fibrotic deposition in the lungs, and reduced the expression of fibroblast markers in mice. In addition, ZBM extract significantly inhibited TGF-β1-induced hyperphosphorylation of FOXO3, and simultaneously improved the low expression level of FOXO3 prototype protein and significantly reduced the phosphorylation level of PI3K-p85 and AKT1, suggesting that ZBM extract improves lung fibrosis by inhibiting the over-activation of PI3K/AKT/FOXO signalling pathway. CONCLUSION: The PI3K/AKT/FOXO signalling pathway is critical for ZBM extract to improve pulmonary fibrosis.