Objective:To investigate the mechanism of geniposide(Gen)in anti-atherosclerosis(AS)through network pharmacology.Methods:We searched authoritative databases such as TCMSP and SwissTargetPrediction to accurately predict and screen out the active targets of Gen.Meanwhile,we comprehensively collected relevant targets of AS with the help of databases such as OMIM and GeneCards.Subsequently,we efficiently identified the intersection targets between AS and Gen through the Venny online tool.To visually display these relationships,we used Cytoscape 3.9.1 software to draw a network diagram of active components and targets.Furthermore,we utilized the STRING and Metascape databases to deeply analyze protein-protein interactions(PPI)and target enrichment.Finally,we simulated molecular docking of key targets using SYBYL-X 2.0 software.Results:A total of 171 active targets for Gen and up to 5 646 targets for AS were predicted.Among them,we discovered 118 intersection genes.Further analysis revealed that Gen exerts its therapeutic effects on AS primarily by mediating the mitogen-activated protein kinase(MAPK)signaling pathway and influencing key targets such as interleukin-6(IL-6),interleukin-1β(IL-1β),and epidermal growth factor receptor(EGFR).The results of molecular docking further confirmed that Gen has excellent binding capabilities with targets such as MAPK14,JUN,and PTEN.Conclusion:This study suggests that Gen may play a crucial role in the treatment of AS by affecting genes such as MAPK14,JUN,and PTEN through the MAPK signaling pathway.This discovery not only provides new insights into the treatment of AS but also lays a solid foundation for subsequent experimental research.