Network pharmacology,molecular docking and animal experimental studies were used to investigate the mechanism of dihydromyricetin (DHM) in improving renal fibrosis in type 2 diabetic db/db mice.Initially,a 10-week DHM intervention was observed to ameliorate renal fibrosis in db/db mice.The chemical structure and targets of DHM were further obtained by TCMSP and PharmMapper,and the disease targets were retrieved by DisGeNET database.Venn analysis was performed on DHM targets and disease targets,and the intersection targets were uploaded to the String database to construct the PPI network.The ′drug-target-disease′ network was constructed by Cytoscape software.The GO enrichment analysis and KEGG enrichment analysis of the intersection target genes were performed by the David database.At the same time,the top 10 intersection targets of PPI network were visualized,and the top 5 intersection targets were subjected to molecular docking with DHM using PDB database,Pymol software and AutoDock Tools software.The first core target AKT and related signaling pathways were verified by Western blot.Animal experiments showed that DHM intervention could reduce the body weight of db/db mice and improve the levels of blood glucose,creatinine,urea nitrogen and urine protein in db/db mice.HE,Masson and PAS staining showed that renal fibrosis of db/db mice was alleviated.In addition,a total of 37 intersections of drugs and disease targets were obtained by network pharmacology,300 GO-related items and 108 related pathways were obtained by enrichment analysis.Molecular docking results showed that DHM could spontaneously bind to key targets.Western blot analysis results showed that DHM intervention could reduce the protein expression of Notch1,NICD,Hes1 and Hey1 in the kidney of db/db mice,up-regulate the level of PTEN protein,inhibit the phosphorylation of AKT,thus improve renal fibrosis.Taken together,DHM may alleviate renal fibrosis in db/db mice by regulating Notch/PTEN/AKT pathway.