Endothelial progenitor cells (EPCs) have important effect in tissue repair in ischemic organs. The present study was conducted to demonstrate the mobilization of EPCs and its possible mechanism after acute ischemic stroke (AIS). A total of 148 individuals were examined, including 106 patients with ischemic stroke and 42 healthy controls. Seventy-one patients with imaging-confirmed AIS were examined at days 1, 7, 14, and 21 after stroke onset. Circulating EPCs were quantified by flow cytometry using CD133 and KDR surface markers. Serum stromal cell-derived factor-1 (SDF-1) concentrations were determined by enzyme-linked immunosorbent assay. Patients with AIS had significantly lower EPC level than that in the controls (0.022 ± 0.013 vs 0.051 ± 0.020; p < 0.01). This difference did not remain significant after adjusting for risk factors at multivariate analysis. Blood pressure, triglyceride, low-density lipoprotein (LDL), and fasting blood sugar were inversely correlated with EPC levels (p < 0.01). Systolic blood pressure and LDL remained independent predictors of baseline EPC levels. The number of circulating EPCs increased on day 7 after AIS, reached a peak on day 14, and decreased on day 21. The concentration of SDF-1 had similar changes. The increment of EPCs was correlated with the infarct volume (r = 0.708; p = 0.006) and SDF-1 concentration on day 14 (r = 0.714; p < 0.001). Baseline EPC level in patients with AIS reflects the cumulative vascular endothelial damage. EPCs could be mobilized into peripheral circulation in response to stroke stress. This mobilization was associated with the increased expression of SDF-1.