OBJECTIVE: To study the effects of valsartan on perionstin and AP-1 during renal tubular epithelial cell-mesenchymal tissue (EMT) transformation under the condition of high glucose. METHODS: Human renal tubular epithelial cells (HK-2 cells) were cultured in vitro under the condition of high glucose, and then divided into blank control group, valsartan high-dose, middle-dose and low-dose groups (10-3, 10-4,10-5 mol/L); normal control group was set up. They were treated for 48 h. The morphology of HK-2 cells was observed; cell viability (OD value) of HK-2 cells were detected, and the content of Ⅲ type collagen, the protein expression of AP-1 and mRNA expression of Periostin and AP-1 were detected. RESULTS: Compared with normal control group, intercellular space of HK-2 cells enlarged and HK-2 cells were separated from nearby cells; exuberant cellular fission, cell viability, the content of Ⅲ type collagen, the protein expression of AP-1, mRNA expression of periostin and AP-1 were strengthened in other group (P<0.05). Compared with blank normal group, cell viability, the content of Ⅲ type collagen, the protein expression of AP-1, mRNA expression of periostin and AP-1 were lower in valsartan high-dose, medium-dose and low-dose groups (P<0.05), especially in valsartan medium-dose group (P<0.01). CONCLUSIONS: High glucose can promote EMT of HK-2 cells. Valsartan can down-regulate the protein expression of Periostin in renal tubular epithelial cell and slow down EMT via inhibiting the expression of AP-1.