Platelet activation has a critical role in arterial disorders. In this study, we showed that the upregulation of P-selectin expression on platelets was related with clinical worsening in acute ischemic stroke. We serially (within 24 hr, at 72 hr, and 7 days) measured the expression of P-selectin on platelets in patients with acute ischemic stroke (n=45) and investigated the correlation between their extents and clinical severity of ischemic stroke. A significant relationship between the P-selectin expressions and National Institute of Health Stroke Scale (NIHSS) was observed at 72 hr and 7 days after ischemic stroke onset. Patients with clinical deterioration showed significantly increased expression of P-selectin on platelets as compared to those without deterioration. These results suggest that the P-selectin expression on platelets may contribute to the aggravation of clinical course in acute ischemic stroke. Thus, adequate manipulation of activated platelets is an important therapeutic strategy in acute ischemic stroke.