To investigate the main active components,the potential targets and molecular pathways of Mori Cortex in the treatment of diabetic peripheral neuropathy (DPN) by using network pharmacology-molecular docking,and to explore the mechanism of Mori Cortex treating on DPN.The main active components and the gene targets of Mori Cortex were screened from the Chinese Medicine System Pharmacology Database (TCMSP).DPN targets genes were screened by searching the following databases of GeneCards database and OMIM database.Using the Cytoscape software to construct the Chinese herbs regulatory network diagram of “Chinese herb-active ingredient- target gene-disease”.The active component targets and disease targets were uploaded into the STRING database to construct PPI.We used R language for screening core genes in PPI.GO enrichment and KEGG pathway analysis were performed using R language.The three-dimensional structure and chemical structure of targets and components were obtained from RCSB database.Pymol software was used to remove water and phosphate from protein molecules.AutoDock software was used to convert compound and core protein gene pdb format into pdbqt format and search for active pockets,and finally run AutoDockTools for molecular docking.Enzyme-linked immunosorbent assay (ELISA) and fluorescence spectra were used to verify the results of network pharmacology enrichment analysis.Finally,31 active ingredients and 312 targets were extracted from Mori Cortex,and the highest target counts were quercetin and kaempferol.The core gene in PPI were JUN,MAPK1,RELA,AKT1,IL-6 and so on.GO analysis revealed that it was possibly influenced by the transcriptional activity of corresponding genes,cytokine expression and protein secretion.KEGG pathway analysis also showed enrichment of AGE-RAGE signaling pathway in diabetic complications,Fluid shear stress and atherosclerosis,Kaposi sarcoma-associated herpesvirus infection,MAPK signaling pathway,human cytomegalovirus infection,and TNF signaling pathway.The results of molecular docking showed that the key components have good binding activity with corresponding targets,for example,quercetin.The expression of IL-6 and TNF-α were decreased by ELISA,and the AGEs were decreased by fluorescence spectroscopy.Therefore,Mori Cortex has the characteristics of multi-components,multi-targets,multi-channels and multi-pathways in the treatment of DPN.Its potential mechanism may be related to AGE-RAGE signaling pathway,MAPK signaling pathway,and TNF signaling pathway.