Feifukang (FFK) is a traditional Chinese medicine composed of herbs that protect lung function. However, difficulty arises regarding the clinical application of FFK due to the complex mechanism of Chinese medicines. This study aimed to investigate the efficacy of FFK and explore its targeted genes and pathways. Methods: Histopathological changes and collagen deposition were measured to evaluate the effect of FFK on bleomycin-induced pulmonary fibrosis in mice. The differentially expressed

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... ed genes and pathways were first screened using RNA sequencing. Then network pharmacology and other experiments were conducted to confirm RNA sequencing data. Results: FFK treatment reduced the pathological score and collagen deposition, with a decrease in α-SMA and collagen. RNA sequencing and network pharmacology results all showed that FFK can ameliorate pulmonary fibrosis through multi-genes and multi-pathways. The targeted genes in JAK-STAT signaling pathway are some of the most notable components of these multi-genes and multi-pathways. Further experiments illustrated that FFK regulated phosphorylation of SMAD3, STAT3 and JAK1, and their co-expressed lncRNAs, which all are the important genes in JAK-STAT signaling pathway. Conclusion: FFK can ameliorate pulmonary fibrosis by inhibiting JAK-STAT signaling pathway and has potential therapeutic value for lung fibrosis treatment. Our study provides a new idea for the study of traditional Chinese medicine.