Inflammatory mediators such as cytokines and chemokines are crucially involved in the development of aortic aneurysm. We explored the pathophysiological roles of CCL3 in the development of CaCl2-induced aortic aneurysm by the use of Ccl3-deficient (Ccl3-/-) mice. In the development of aortic aneurysm, CaCl2 was applied to the abdominal aorta of WT and Ccl3-/- mice after laparotomy. After CaCl2 application, the gene expression of Ccl3 was significantly enhanced at 1 and 2 weeks, implying that CCL3 might be involved in the pathogenesis of aortic aneurysm. There was no significant difference in the aortic diameter between WT and Ccl3-/- mice before CaCl2 application. When WT and Ccl3-/- mice were treated with the same manner, the aortic diameter was larger in Ccl3-/- mice than in WT ones. Moreover, the incidence in the aneurysmal development (>50% increase of diameter) was higher in Ccl3-/- mice, compared with WT ones. Histopathologically, the disruption and fragmentation of medial elastic fibers was more evident in the aneurysmal aortic sections of Ccl3-/- mice, compared with WT ones. Immunohistochemically, the infiltration of macrophages but not T lymphocytes in the surrounding tissues of the aorta was significantly enhanced in Ccl3-/- mice compared with WT ones. The enzymatic activity of MMP-9 was significantly enhanced in Ccl3-/- mice compared with WT ones. In vitro, CCL3 treatment apparently decreased gene expression of Mmp9 in WT-derived macrophages. Supportingly, the administration of recombinant CCL3 significantly suppressed in aortic diameter in WT mice at 6 weeks after CaCl2 application compared with controls. Collectively, these observations implied that CCL3 had protective roles in the development of CaCl2-induced aortic aneurysm.