Recently, it has been demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitor or statin can regulate the thrombogenesis beyond its lipid lowering effect. In this study, we investigated the beneficial effect of statin to reduce the platelet P-selectin expression in atherosclerotic ischemic stroke. Thirty-two (28 men, 4 women; mean age 59.8 +/- 9.6 years) patients with atherosclerotic ischemic stroke were assigned to receive simvastatin 20 mg per day for 12 weeks and discontinued for another 12 weeks. Then, administration of simvastatin was discontinued for the following 12 weeks. Using whole blood flow cytometry, we evaluated the change of platelet P-selectin expression of all the patients after the 12-weeks use and the 12-weeks discontinuance of simvastatin. The platelet P-selectin expression was significant reduced after treatment of simvastatin 20 mg for 12 weeks (p < 0.001). However, the effect of statin to reduce platelet P-selectin expression disappeared after 12 weeks of cessation of statin. In addition, the P-selectin changes induced by statin were independent of the changes of the LDL cholesterol (r = -0.311, p = 0.386). This study demonstrated that the use of statin might be a helpful add-on therapy to regulate the platelet related thrombogenesis in atherosclerotic ischemic stroke.