Abstract: Objective To explore the potential mechanism of action of Xuefu Zhuyu Decoction in the treatment of uterine fibroids based on bioinformatics methods.Methods The active ingredients and potential targets of Xuefu Zhuyu Decoction were searched using TCMSP, TCMID, PubChem and other databases. The GEO database was used to screen the differential genes about uterine fibroids. The overlapping targets of Xuefu Zhuyu Decoction for the treatment of uterine fibroid were obtained to construct a protein interaction (PPI) network through STRING database. The key targets involved were screened with Cytoscape software. The GeneOntology functional enrichment analysis and KEGG signaling pathway enrichment were performed with DAID database.Results There were 112 active ingredients in Xuefu Zhuyu Decoction, with 7 434 potential targets, in addition to 1 518 differentially expressed genes associated with uterine fibroid. The Venn diagram illustrated 118 overlapping targets of Xuefu Zhuyu Decoction for the treatment of uterine fibroid, while 30 key targets were screened through the PPI network. Furthermore, GO enrichment analysis mainly involved the positive regulation of MAPK cascade, ERK1 and ERK2 cascade, and cell migration, while KEGG enrichment analysis showed that it mainly involved PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, and tumor necrosis factor (TNF) signaling pathway.Conclusions Xuefu Zhuyu Decoction may reduce inflammation, decrease oxidative stress, and promote neovascularization through the "active ingredient-key target-pathway" effect, which may be effective in the treatment of uterine fibroids.