Abstract: 【Objective】 To investigate the prevention and treatment effect and mechanism of BuPleurum Bupleuri Radix on non-alcoholic fatty liver disease（NAFLD）.【Method】 Chemical constituents and targets of Bupleuri Radix were obtained from TCMSP database and literature review,and disease targets of NAFLD were obtained from Gene Cards and OMIM databases. Protein interaction analysis,KEGG and GO enrichment analysis and molecular docking were performed to screen common targets between Bupleuri Radix and NAFLD,so as to explore potential active components and mechanism of action of Bupleuri Radix against NAFLD. Finally,high fat diet combined with high sugar drinking water was used to establish NAFLD mouse model to verify the therapeutic effect and mechanism of Bupleuri Radix.【Result】 Bupleuri Radix could prevent and treat NAFLD by directly regulating 99 targets through 18 potential active components,of which quercetin,kaempferol and isorhamnetin were the core active components,and AKT1,TNF and ESR1 were the core targets. Enrichment analysis showed that Bupleuri Radix could prevent and treat NAFLD mainly by interfering with PI3K-AKT,MAPK and TNF signaling pathways. The results of animal experiments showed that Bupleuri Radix could reduce the serum AST and ALT levels in NAFLD mice and improve the liver steatosis in NAFLD mice.【Conclusion】 Bupleuri Radix can effectively prevent and control NAFLD,and its mechanism is closely related to the regulation of PI3K-AKT and MAPK signaling pathways.