OBJECTIVE： To study the effect of dihydromyricetin （DMY） on high glucose （HG）-induced glomerular mesangial cell （MCs） proliferation and fibronectin （FN） accumulation， and explore its mechanism for diabetic nephropathy glomerulosclerosis. METHODS： Cells were divided into normal group （5.5 mmol/L glucose）， HG group （30 mmol/L glucose）， DMY low-concentration， medium-concentration， high-concentration groups （30 mmol/L glucose+22.5， 45， 90 μmol/L DMY）. After incubating 48 h， MTT was used to detect the proliferative activity [reflected by the optical density （OD） value] of cells； molecular docking method was adopted to conduct simulation analysis for DMY binding state with Smad2. Cells were divided into normal group （5.5 mmol/L glucose）， HG group （30 mmol/L glucose）， DMY group （30 mmol/L glucose+45 μmol/L DMY） and DMY control group （5.5 mmol/L glucose+45 μmol/L DMY）. After incubating 5 h， Western blot was used to detect the expression levels of phosphorylated Smad2 （p-Smad2） and extracellular matrix protein FN. RESULTS： Results of MTT detection showed， compared with normal group， OD values in HG group were significantly increased （P＜0.05）； compared with HG group， OD values in DMY each concentration group were significantly reduced （P＜0.05）. The Gibbs free energy （ΔG） of DMY and Smad2 protein was －5.64 kJ/mol， Ki was 73.53 μmol/L， and there were hydrogen bond donor and receptor binding in No. 465， 464， 461， 458 amino acid residues. Results of Western blot showed， compared with normal group， expression levels of p-Smad2 and extracellular matrix protein FN in HG group were significantly increased （P＜0.05）； compared with HG group， expression levels of p-Smad2 and extracellular matrix protein FN in DMY group were significantly decreased （P＜0.05）. CONCLUSIONS： DMY inhibits HG-induced MCs proliferation and improves diabetic nephropathy glomerulosclerosis by combining with Smad2 and inhibiting Smad2 phosphorylation to reduce the extracellular matrix protein FN expression.