Abstract: Objective To verify whether Rosuvastatin could inhibit vascular smooth muscle cell (VSMC) phonotype switch by down-regulation of KLF-4. Methods The primary culture and identification of SD rat VSMCs were conducted, VSMCs in the 3rd to 5th passages were used for the following experiments. After treatment with different concentrations of Rosuvastatin, MTT was used to investigate the proliferative ability of VSMCs. Transwell chambers and wound healing were employed to test the migration ability of VSMCs. IHC was used to detect the expression of SM-actin and the morphological structure of VSMCs. Western blot was used to investigate the expressions of SM-actin, SM-MHC, SM-22α, osteopontin (OPN) and KLF-4 in VSMCs. After KLF-4 was transfected into VSMCs, the metheods were used again to test the phonotype changes of the VSMCs. Results Compared with the control group, the migration and proliferation ability of the VSMCs were decreased in the Rosuvastatin group. The expressions of SM-actin, SM-22α and SM-MHC in the Rosuvastatin group were significantly increased (P < 0.05), and the expression of OPN also increased (P < 0.05). IHC showed the VSMCs in the Rosuvastatin group became thinner and longer than those of the control group. After KLF-4 was transfected into VSMCs, the proliferation and migration ability of the VSMCs increased (P < 0.05). Overexpression of KLF-4 reversed the effect of Rosuvsatatin on VSMCs phonotype transformation. Conclusions Rosuvastatin inhibits VSMCs phonotype switch by down-regulation of KLF-4.