The aim of this study was to investigate the dynamic changes in plasma decorin concentration after acute ischemic stroke and to study its relationship with clinical stroke subtypes. We collected three plasma samples from patients with acute ischemic stroke (n = 35) and controls (n = 30): upon admission (1-3 days) between 3 days and 1 week (3-7 days), and between 7 days and 2 weeks (7-14 days). The relationship between Decorin concentration and Trial of ORG10172 in Acute Stroke Treatment (TOAST) subtypes and outcomes were evaluated. The concentration of decorin gradually decreased following the onset of stroke at all different time-points (<3 days, p < 0.05; 3-7 days, p < 0.01; and 7-14 days, p < 0.01) compared to controls. The level of decorin at 7-14 days is significantly lower than that at <3 days (p < 0.01) in the stroke patients. Decorin levels were lower in the Large-artery atherosclerosis group than the rest of the TOAST subgroups (p = 0.024). Decorin levels decreased more in the patients with poor outcome (mRS 3-6) than those with favorable outcome (mRS 0-2, p < 0.05) at a time-point of 3-7 days. There is a dynamic reduction in Decorin level the days following ischemic stroke, and the decrement persists at least the first 2 weeks. The dynamic reduction of decorin might indicate that decorin is concomitantly involved in the pathophysiological processes of stroke. Larger studies are needed to confirm whether decorin is a useful marker of stroke and a prognostic indicator of outcome.