Aim To study the effects of AMD3100 on atherosclerosis and the possible mechanism in apolipoprotein E-/-mice. Methods 12 male apolipoprotein E-/-mice,8 weeks old,were randomly divided into two groups: AMD3100 group(2.5 mg/kg,the next day intraperitoneal injection) and control group(PBS 0.1 mL,the next day intraperitoneal injection).After fed with high fat and cholesterol western food for 12 weeks,all mice tissue specimen and bone marrow cells were harvested.The Hematoxylin/Eosin staining of paraffin section was performed to detect atherosclerotic plaque of aortic root.By counting the typical endothelial progenitor cells-colony forming units(EPC-CFU) and observing the size and cell density of secondary EPC-CFU,the clonality of endothelial progenitor cells was measured.The expression of CXCR4 mRNA and protein were examined by RT-PCR and Western blotting. Results Compared with control group,the area percentage of atherosclerotic lesion and vessel lumina increased 38.8% in AMD3100 treated apolipoprotein E-/-mice(37.2%±3.6% vs 26.8%±2.5%,P<0.05).The clonality of endothelial progenitor cells derived from AMD3100 group decreased in comparison to control group(primary EPC-CFU: 9.67±2.16 vs 21.83±2.64,secondary EPC-CFUs: 1.67±0.31 vs 4.11±0.65;P<0.01).The expression of CXCR4 mRNA and protein of AMD3100 group were also reduced(P<0.01). Conclusions The atherosclerotic lesion was aggravated by administration of AMD3100 in apolipoprotein E-/-mice.Possible mechanism of this action for AMD3100 are associated with the inhibition of the clonality of bone marrow endothelial progenitor cells and down-regulatipon of CXCR4 expression on endothelial progenitor cells.