To study the effect of AMD3100 on the mobilization, proliferation, migration and adhesion of endothelial progenitor cells (EPC), EPC was isolated from apoE^-/- mice bone marrow, 12 male apoE^-/- mice, with 8 weeks old,were randomly divided into two groups, AMD3100 group (2.5mg / (kg·2d)) and control group(PBS,0.1 ml/2d). After feeding western (high fat and cholesterol) for 12 weeks, the bone marrow cells were isolated and cultured by way of differential-speed-adherence and Micropore-Method. CD133⁺ VEGFR-2⁺ bone marrow cell was identified as endothelial progenitor cells by immunofluorescence. The proliferation, migration and adhesion of endothelial progenitor cells were detected by MTT chromometry, transwell and adhesion test, respectively. By counting the typical endothelial progenitor cells-colony forming units (EPC-CFUs) and observing the size and cell density of second EPC-CFUs, the clonality of endothelial progenitor cells was determined. The expression of CXCR4 mRNA and protein were measured by RT-PCR and Western blot. As a result, the proliferation, migration, adhesion and clonality of endothelial progenitor cells derived from AMD3100 group were attenuated in comparison to the control group; the expression of CXCR4 mRNA and protein of AMD3100 group were also lower to control group. It can be concluded that, lasting administration of AMD3100 inhibits the proliferation, migration, adhesion and clonality of bone marrow endothelial progenitor cells and down-regulate the expression of CXCR4 on endothelial progenitor cells.