This study aims to investigate the targets and mechanisms of hydroxysafflower yellow A (HSYA) in the treatment of pulmonary fibrosis (PF) based on network pharmacology and animal experiments.Network pharmacology databases such as SwissTarget Prediction,PharmMapper,GeneCards,OMIM,and TTD were used to screen the targets of HSYA and PF,common target and protein-protein interaction (PPI) network were obtained by the intersection.Using the DAVID database for GO and KEGG enrichment analysis,to explore the possible molecular mechanisms of HSYA treatment for PF.The mouse model of pulmonary fibrosis was established by bleomycin.The morphology of lung tissue was observed by HE and Masson staining,and the content of hydroxyproline (HYP) in lung tissue was detected;Immunohistochemistry and Western blot were used to detect the proteins related to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway in mouse lung tissue.The network pharmacology method screened 132 common targets for drug diseases;GO enrichment analysis yielded 719 entries while KEGG pathway enrichment analysis screened 160 signaling pathways,mainly involving PI3K-AKT,Ras,MAPK and other signaling pathways.IHC and Western blot results showed that the protein expression of PI3K,AKT,and mTOR in the lung tissue of the HSYA group was significantly reduced compared to the model group (P<0.01).Network pharmacology analysis and animal experimental results suggest that HSYA may affect the pathogenesis of PF by regulating the PI3K/AKT/mTOR signaling pathway,providing scientific basis for the clinical application of HSYA.