Objective:This is the first study to explore the mechanism of colchicine in treating coronary artery disease using network pharmacology and molecular docking technology, aiming to predict the key targets and main approaches of colchicine in treating coronary artery disease. It is expected to provide new ideas for research on disease mechanism and drug development.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Swiss Target Prediction and PharmMapper databases were used to obtain drug targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DrugBank and DisGeNET databases were utilized to gain disease targets. The intersection of the two was taken to access the intersection targets of colchicine for the treatment of coronary artery disease. The Sting database was employed to analyze the protein-protein interaction network. Gene Ontology (GO) functional enrichment analysis was performed using Webgestalt database. Reactom database was applied for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was simulated using AutoDock 4.2.6 and PyMOL2.4 software.Results:A total of 70 intersecting targets of colchicine for the treatment of coronary artery disease were obtained, and there were interactions among 50 targets. GO functional enrichment analysis yielded 13 biological processes, 18 cellular components and 16 molecular functions. 549 signaling pathways were obtained by KEGG enrichment analysis. The molecular docking results of key targets were generally good.Conclusion:Colchicine may treat coronary artery disease through targets such as Cytochrome c (CYCS), Myeloperoxidase (MPO) and Histone deacetylase 1 (HDAC1). The mechanism of action may be related to the cellular response to chemical stimulus and p75NTR-mediated negative regulation of cell cycle by SC1, which is valuable for further research exploration. However, this research still needs to be verified by experiments. Future research will explore new drugs for treating coronary artery disease from these targets.