In this study,network pharmacology,molecular docking and experimental verification were used to explore the mechanism of Sappan Lignum in the treatment of diabetic peripheral neuropathy (DPN).The chemical professional database,ETCM database and literature were used to query the components of Sappan Lignum,the active components of Sappan Lignum were screened by SwissADME platform,and the potential targets were predicted by PharmMapper database.At the same time,the targets related to DPN disease were screened from GeneCards,DrugBank and OMIM databases,and the intersection targets were selected.The protein interaction relationship was obtained by STRING11.5,and the component-target protein interaction network was constructed by Cytoscape 3.8.2 software.Then GO and KEGG enrichment analysis was carried out through Metascape database,and molecular docking was carried out by Autodock combined with Pymol,At the same time,the anti-DPN inflammation and oxidation effects of Sappan Lignum extract were experimentally verified.Finally,a total of 93 active components of Sappan Lignum were screened out,and 109 key targets for treating DPN were identified.Among them,rhamnetin,brazilin,brazilein, sappanchalcone,butein, quercetin and other components have the effect of improving peripheral neuropathy,which may be through estrogen receptor alpha(ESR1),insulin-like growth factor-1(IGF1),Caspase 3(CASP3),peroxisome proliferator activator receptor gamma(PPARG),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9 (MMP-9),epidermal growth factor receptor(EGFR),RAC-alpha serine/threonine-protein kinase(Akt1),albumin(ALB),proto-oncogene tyrosine-protein kinase src(SRC) and other targets mediate PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway and HIF.Molecular docking verification showed that the active components had good docking activity with AKT1,CASP3 and MMP-9.It was found that Sappan Lignum extract could reduce the contents of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6) and monocyte chemoattractant protein-1(MCP-1),and increase the content of serum SOD.This study found that Sappan Lignum played an intervention role in the treatment of DPN through multi-components,multi-targets and multi-pathways,which provides a new direction for the basic and clinical research of Sappan Lignum in the treatment of DPN.