Abstract： Objective： To explore action mechanism of Ruxian Xunxi Prescription (a prescription for fumigation and washing on breast) in treating postoperative wound healing after non-puerperal mastitis (NPM) surgery using network pharmacology， and verify key signaling pathways through clinical research. Methods：The key compound components and action targets of Ruxian Xunxi Prescription were searched in the Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP). Common targets associated with breast wound healing were identified in the Human Gene Database (Genecards)，which were entered into STRING database to obtain the protein-protein interaction (PPI) networks，and the PPI networks were then mapped via Cytoscape 3.10.10 software. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for potential disease - medicine targets through DAVID and Metascap databases. The protein expression levels of vascular endothelial growth factor (VEGF) and signal transducers and activators of transcription 3 (STAT3) were detected by Western Blot in four patients after NPM surgery. Results： There were 101 targets involved in promoting wound healing with Ruxian Xunxi Prescription， among which the key targets were mainly divided into matrix metalloproteinases (MMP2， MMP9)， cytokines [interleukin (IL) - 1β， IL-6， epidermal growth factor receptor (EGFR)， transforming growth factor - β (TGF - β)， tumor necrosis factor (TNF)， fibroblast growth factor 2(FGF-2)]， adhesion molecules (ICAM-1) and signal transduction protein (STAT3，MAPK)，ect. ，involving in the regulation of signaling pathways such as VEGF，hypoxia-inducible factor-1 (HIF-1)， IL-17， AGE-RAGE， TNF， etc. . After treatment， the protein expression levels of VEGF and STAT3 in wound tissues after NPM surgery were increased when compared with those before treatment (P＜0.05). Conclusion： Network pharmacology and clinical studies have confirmed that Ruxian Xunxi Prescription exerts a curative effect on promoting postoperative wound healing after NPM surgery through multi-channel and multi-target synergistic regulation.