Objective: To predict the effective components, potential targets and pathways of Simiao Yong’an Decoction in the treatment of lower extremity arteriosclerosis obliterans (ASO) based on the method of network pharmacology, and to explore the mechanism of Simiao Yong’an Decoction in treating ASO combined with cell experiment. Methods: TCMSP database was used to screen the active components and targets of Simiao Yong’an decoction, and Genecards and OMIM databases were used to obtain ASO related proteins; PPI network of drug disease target proteins was constructed by string platform; go function and KEGG pathway enrichment of Simiao Yong’an Decoction ASO target were analyzed by David database. The drug target pathway with high correlation with ASO was selected. The model of vascular smooth muscle cell injury (VSMCs) induced by ox LDL was used, and Simiao Yong’an decoction containing pharmaceutical Qing was given to verify the therapeutic effect of Simiao Yong’an Decoction on ox LDL induced VSMCs and its regulation on highly correlated target pathway. Results: A total of 126 active components of Simiao Yong’an Decoction were screened, 40 targets of Simiao Yong’an Decoction ASO were selected, 99 go biological processes and 48 related signal pathways were related to ASO; the experimental results showed that with the passage of time, Simiao Yongan decoction could significantly inhibit the proliferation of VSMCs (P<0.05); compared with the model group, the percentage of BrdU positive cells in each dose group of Simiao Yong’an decoction was significantly higher than that in the model group In addition, Simiao Yong’an decoction could significantly inhibit the proliferation of VSMCs (P<0.05); in addition, Simiao Yongan decoction could inhibit the levels of IL-6 and IL-1β (P<0.05); significantly inhibit the expression of PCNA, JAK2 and STAT3 mRNA (P<0.05); Conclusions: Simiao Yong’an decoction has the effect of “multi-component, multi-target and multi-channel” in the treatment of ASO. It can inhibit the activation of JAK/STAT signaling pathway, play an anti-inflammatory role and inhibit the proliferation of vascular smooth muscle cells.