Objective:To explore the effect of Rho-kinase signal pathway in renal interstitial fibrosis of diabetic nephropathy(DN)and the mechanism of fluvastatin in the prevention of renal interstitial fibrosis of DN. Methods:Human renal proximal tubular epithelial cells(HK-2 cells)were cultured in vitro. Rho-kinase activity was expressed as phosphorylation of myosin-phosphatase target-1(p-MYPT-1). The level of p-MYPT-1 and fibronectin(FN) stimulated by high glucose was determined by Western blot at the time of 0 h,6 h,12 h and 24 h after treatment. Same markers were detected when HK-2 cells cultured with high glucose treated with different concentrations(10-7,10-6 and 10-5 mol/L)of fluvastatin for 12 h and treated by lysophosphatidic acid(LPA) further. Results:High glucose enhance the expression of p-MYPT-1 and FN in culured HK-2 cells at the time of 6 h,12 h and 24 h,compared with the time of 0 h. The increase of FN expression stimulated by high glucose was time-dependent and the increased level of p-MYPT-1 reached the peak at 12 h. Fluvastatin decreased the level of p-MYPT-1 and FN induced by high glucose in a dose-dependent manner. The inhibitory effect of fluvastatin on up-regulation of p-MYPT-1 and FN stimulated by high glucose can be reversed by LPA. Conclusion:Rho-kinase may be one of the initiation signals of renal interstitial fibrosis of DN. Fluvastatin can prevent the development of renal interstitial fibrosis of DN by inhibiting Rho-kinase signaling pathway.