Abstract: OBJECTIVE To explore the effects of modified Cangfu Daotan decoction(CFDTD) on insulin resistance(IR) in polycystic ovarian syndrome(PCOS) rats based on network pharmacology analysis. METHODS TCMSP, TCM database@Taiwan, Drugbank and GeneCards databases were used to screen out the active chemical components and action targets of CFDTD. TTD, PubMed, and PharmGKB databases were used to screen out the disease targets associated with PCOS. After mapping the component target with the disease targets, the Cytoscape 3.7.1 software was used to construct the component-target interaction network of CFDTD. Next, STRING and Cytoscape software was used to construct protein-protein interaction network and identify the hub targets. Subsequently, Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis was performed by using the ClueGO plug-in tool in Cytoscape. Furthermore, experimental validation was conducted in the PCOS with IR model rats induced by letrozole combined with high-fat and high-sugar diet. The treated groups were given CFDTD at a dose of 15 and 30 g·kg^-1·d^-1, and metformin hydrochloride(MH, 50 mg·kg^-1·d^-1) respectively, the control and PCOS groups were given equivoluminal normal saline for 4 weeks. The serum levels of fasting blood glucose(FPG), fasting insulin(FINS), follicle stimulating hormone(FSH), luteinizing hormone(LH), testosterone(T) and estradiol(E₂) of rats were detected by automatic chemical analyzer, and the homeostatic model assessment insulin resistance index(HOMA-IR) was then calculated. HE staining was used to observe the morphological changes of ovarian tissues. The protein expression levels of insulin receptor(INSR), insulin-like growth factor-I(IGF-I), insulin-like growth factor-I receptor(IGF-IR), insulin(INS), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) were detected by Western blotting. RESULTS The 86 active components of CFDTD and 126 potential targets related to PCOS were screened by network pharmacology analysis. KEGG analysis showed that the potential targets were closely related to signaling pathway such as insulin resistance, steroid hormone biosynthesis, ovarian steroidogenesis, estrogen signaling pathway, PI3K-Akt signaling pathway, type II diabetes mellitus, etc. Protein interaction analysis indicated that INS, TNF-α, and IL-6 were the hub targets of protein interaction network. Compared with the PCOS group, the levels of FPG, FINS, HOMA-IR, LH, T and E₂ in the treated groups decreased significantly(P all<0.01), and the damaged degree of ovarian tissue was significantly reduced. Western blotting showed that CFDTD could significantly decrease the protein expression levels of INSR, IGF-IR, INS, TNF-α, and IL-6. CONCLUSION CFDTD can improve the IR in PCOS rats by downregulate the protein expression levels of INSR, IGF-IR, INS, TNF-α, and IL-6.