Abstract：Objective：To explore the mechanism of Gancao Xiexin Decoction in treating type 2 diabetes mellitus (T2DM) skin injury based on network pharmacology. Methods： The active ingredients and target genes of each Chinese medicinal of Gancao Xiexin Decoction were screened through TCMSP， Pubchem database， Swiss Target Prediction and Uniprot database； the disease targets of T2DM were retrieved through GeneCards， CTD and OMIM databases， and the disease targets of skin injury were retrieved through GeneCards and OMIM databases. The cross-targets of Gancao Xiexin Decoction and T2DM skin injury were obtained by intersection of the above three groups of targets， and the Venn diagram of medicinal-disease cross-targets was made. Cytoscape 3.9.1 software was used to construct the active ingredients of Gancao Xiexin Decoction-T2DM skin injury cross-targets network graph. The protein-protein interaction (PPI) network was constructed through STRING database，and the core targets of PPI network were screened by Cytoscape 3.9.1 software. The Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out through DAVID database. Results：A total of 1 080 active medicinal targets，3 001 T2DM disease targets，617 skin injury disease targets， and 47 cross-targets of Gancao Xiexin Decoction-T2DM skin injury were obtained. The Gancao Xiexin Decoction-T2DM skin injury cross-targets network graph revealed that quercetin， kaempferol，isorhamnetin glabridin，and licoisoflavone were important active ingredients of Gancao Xiexin Decoction in treating T2DM skin injury. The PPI network analysis revealed that epidermal growth factor receptor (EGFR)， tumor protein 53 (TP53)， vascular endothelial growth factor A (VEGFA)， Catenin β1， matrix metalloproteinase-9， epidermal growth factor， phosphatase and tensin homolog， intercellular adhesion moleclar-1 and transforming growth factor β1 were core targets of Gancao Xiexin Decoction in treating T2DM skin injury. The GO functional enrichment analysis revealed that Gancao Xiexin Decoction in treating T2DM skin injury may play a role by affecting VEGF receptor signaling pathway，response to insulin， positive regulation of mitogen-activated protein kinase (MAPK) activity，inflammatory response，apoptosis and other biological processes. The KEGG pathway enrichment analysis revealed that Gancao Xiexin Decoction may treat T2DM skin injury through pancreatic cancer， advanced glycation end productsreceptor for advanced glycation end product (AGE-RAGE) signaling pathway， focal adhesion， MAPK signaling pathway， pathways in cancer， PI3K-Akt signaling pathway and other important signaling pathways. Conclusion： Quercetin， kaempferol， glabridin and other constituents in Gancao Xiexin Decoction can regulate AGE-RAGE， MAPK， PI3K-Akt and other signaling pathways through EGFR， MMP9，TP53 and other targets in treating T2DM skin injury.