Background: The CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells ( SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated. Methods: We here have orthotopically transplanted infrarenal Cx3cr1(-/-) Apoe(-/-) and Cx3cr1(+/+) Apoe(-/-)aortic segments into Apoe(-/-) mice, as well as Apoe(-/-) aortic segments into Cx3cr1(-/-) Apoe(-/-)mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet. Results: Transplantation of Cx3cr(-/-) Apoe(-/-) aortic segments into Apoe(-/-) mice resulted in reduced atherosclerotic plaque formation compared to plaque size in Apoe(-/-) or Cx3cr1(-/-) Apoe(-/-) mice after transplantation of Apoe(-/-) aortas. This reduction in lesion formation was associated with reduced numbers of lesional SMCs but not macrophages within the transplanted Cx3cr(-/-) Apoe(-/-) aortic segment. No differences in frequencies of proliferating and apoptotic cells could be observed. Conclusion These results indicate that CX3CR1 on resident vessel wall cells plays a key role in atherosclerotic plaque formation in transplanted aortic grafts. Targeting of vascular CX3CL1/ CX3CR1 may therefore be explored as a therapeutic option in vascular transplantation procedures.