Objective To investigate the effects of Huangqi Tujian Mixture on the proliferation of glomerular mesangial cells in rats under high-glucose condition and its possible mechanism.Methods Male SD rats were randomly divided into two groups,which were respectively given Huangqi Tujian Mixture and distilled water of equal volume in order to prepare serum contained drug and normal rat serum.The glomerular mesangial（HBZY-1） cells of rats were randomly divided into four groups: 5 mmol/L glucose+normal serum group（control group）, 25 mmol/L mannitol + normal serum group（D-mannitol group）, 30 mmol/L glucose + normal serum group group（HG group） and 30 mmol/L glucose + drug-contained serum group（HG+HQTJM group）.After 24 hours, 48 hours and 72 hours of intervention, CCK8 method was used to detect the proliferation activity and western blot method was used to detect the protein expression changes of collagen Ⅳ and fibronectin in HBZY-1 cells in each group.Meanwhile, the mRNA expressions of tumor necrosis factor-α,Interleukin-1β,phosphatase and tensin homologue deleted on chromosome 10 and protein kinase B in HBZY-1 cells were detected by real time PCR, the expression levels of TNF-α and IL-1 β in the supernatant were measured by Elisa.Results Compared with the control group, D-mannitol group had no significant effect on the proliferation of HBZY-1 cells and the expression of various molecules had no statistical significance（P>0.05）, while in the HG group, the proliferation activity of HBZY-1 cells at 48 h and 72 h of intervention increased significantly, the protein expression of COLIV and FN increased, the gene expression of TNF-α, IL-1β and Akt increased significantly（P<0.05）, and the mRNA expression of PTEN decreased with the difference not statistically significant（P>0.05）, the expression of TNF-α and IL-1β protein in the supernatant of HG group significantly increased（P<0.05）.Compared with the HG group, the HG+HQTJM group could significantly inhibit the proliferation of HBZY-1 cells（P<0.05）and the expression of COLIV and fibronectin in mesangial cells after 72 hours’ intervention;the mRNA expression of TNF-α in drug contained serum group was significantly lower than that in HG group after 24 hours’ intervention（P<0.05）, and the mRNA expression of IL-1β was obviously lower than that of HG group after 48 hours’ and 72 hours’ intervention（P<0.05）.In HBZY-1 cells, the PTEN gene expression significantly increased, Akt gene expression decreased, and TNF-α and IL-1β protein expression in cell culture supernatant increased at three time points of intervention（P<0.05）.Conclusion Huangqi Tujian Mixture can significantly reduce the proliferation activity of HBZY-1 cells and down-regulate the protein expression of COLIV, FN in mesangial cells under high-glucose condition, which may be related to the activation of PTEN and the inhibition of inflammation mediated by PI3 K/AKT pathway.