Objective To explore the effect and preliminary mechanism of plant extract ursolic acid(UA)inreducing hepatic ischemia/reperfusion injury(HIRI). Methods C57 male mice were divided into sham operation group,sham operation +UA group,HIRI group,HIRI low-dose group and HIRI high-dose group. The analysis and validationwere carried out by methods such as animal experiments,network pharmacology and molecular biology. Results Animal experiments showed that UA significantly reduced the activities of AST and ALT in serum of HIRI mice. Target genescorresponding to HIRI and ursolic acid were obtained by TCMSP,Pharm Mapper,Swiss Target Prediction,GeneCards and other databases,and key target genes were obtained by DAVID,STRING and Cytoscape. They were PPARG (peroxisome proliferator-activated receptor gamma,PPARG),
MAPK3(mitogen-activated protein kinase 3,MAPK3) and PTGS2(prostaglandin G/H synthase 2,PTGS2). Finally,PTGS2 was identified as the hub target gene in this study according to the molecular docking score and the number of hydrogen bonds binding between receptor and ligand. Compared with Sham operation group,PTGS2 was highly expressed in HIRI group(P < 0.01). Compared with HIRI group,the expression of PTGS2 in HIRI + LUA and HIRI + HUA groups was significantly decreased (P < 0.01). Conclusion UA can regulate the protective effect of PTGS2 on hepatic ischemia reperfusion injuryin mice. Thisstudy providesa reference for clinical development of new drugsto interveneHIRI.