Abstract: OBJECTIVE To explore the synergistic mechanism of Liuwei Dihuang pill in the treatment of diabetic nephropathy(DN) by using network pharmacology and molecular docking method. METHODS The active ingredients and corresponding targets of Liuwei Dihuang pills were screened out by searching multiple databases and literature. With the help of Genecard, OMIM and Drugbank databases, the targets of diabetic nephropathy were collected and the drug-disease joint targets were screened through Venny 2.1 software. Subsequently, STRING and Cytoscape software was used to analyze and construct protein-protein interaction network, and use CytoNCA plug-in for topology analysis to select core targets. Then, the GO Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed by using ClueGO tool. Finally, the binding capacity between active components and key targets was validated by molecular docking using AutoDock. RESULTS Forty active components involved in 128 targets related to DN were identified in Liuwei Dihuang pill. Especially by regulating 28 core targets, participating in the regulation of biological processes such as gene transcription, apoptosis and proliferation, signal transduction, inflammation, and protein phosphorylation in the body, intervening in tumors, AGE-RAGE, IL-17, MAPK, signal pathways such as HIF-1 and Toll-like receptors to play a role in the treatment of DN. The molecular docking verified that the 5 active compounds had reliable affinity with corresponding targets. CONCLUSION The treatment of DN with Liuwei Dihuang pill has the characteristics of multi component-multi target-multi pathway, which provides new ideas and new directions for further research on the molecular mechanism of Liuwei Dihuang pill in the treatment of DN.