Aims: Hypercholesterolemia is known to impair EPC���s function. However the effect of HMG Co-A reductase inhibitor for angiogenesis & function of EPC was controversial. To verify the mobilizing effect & its mechanism of HMG Co-A reductase inhibitor to EPC in human in vivo, we evaluate the number of EPC from peripheral blood MNC, type of mobilized cell and increased serum cytokine in hypercholesterolemic patients before & after statin treatment. Methods: 22 hypercholesterolemic patients were included. MNCs were isolated at pre- & post-statin treatment (simvastatin 20mg/day,4weeks), and cultured with EGM-2 MV. EPCs were identified by UEA-1 lectin & DiI-acetylated LDL uptake. Serial changes of EPCs were observed at 4 random HPFs. Mobilized cell type was evaluated immediately by FACS. Serum IL-8 was evaluated at pre- & post-statin. For the role of monocyte, monocyte secreting IL-8 after simvastatin-treatment & immunoblot analyses of glycogen synthase kinase-3棺(GSK), 棺-catenin were evaluated. Results: In post-statin, EPCs were increased in number (p<0.05). 2 types of EPC, early EPC with lower proliferative activity & late EPC with higher proliferative activity, were observed. Late EPC was observed more and earlier in post-statin than pre-statin (8/22 vs 4/22, D15짹3 vs D38짹21). KDR(+) cell was significantly increased in post-statin (37 vs 87 %, P<0.05). Post-statin serum IL-8 was increased, well correlated with manifestation of late EPC(161짹70 vs 49짹32 pg/ml,p<0.05). In vitro study of simvastatin-treated EPC, IL-8 of conditioned media at early EPC was higher than late EPC(47568짹1190 vs 7073짹125 pg/ml,P<0.05). Simvastatin-treated monocyte showed higher IL-8 expression than vehicle. Immunoblot analysis of simvastatin-treated monocyte showed increased p-GSK and 棺-catenin expression. Conclusion; These findings suggest the role of simvastatin mobilizing EPC, especially KDR(+) cells in humans. Higher human in vivo post-statin IL-8 level with late EPC and higher in vitro IL-8 level of early EPC than late EPC suggest the role of early EPC���s angiogenic cytokine for angiogenesis & late EPC manifestation. This mobilizing effect was mediated IL-8 and GSK-棺-catenin pathway through monocyte