The participation of inflammatory cells in atherosclerosis is a well-known process that involves numerous molecules including chemotactic cytokines (chemokines) for their entry into the vessel wall. Although the C-C chemokine monocyte chemoattractant protein-1 and its receptor, CCR2, have been implicated in atherosclerosis, the role of the classic C-X-C chemokine, interleukin-8 (KC/growth-related oncogene alpha in mice) and its receptor CXCR2 has not been studied in the pathogenesis of atherosclerosis. Our research has shown that CXCR2 is strongly expressed on macrophages (Mphi) in atherosclerotic lesion. This CXCR2 expression is proatherogenic in that CXCR2 deficiency significantly reduces the progression of advanced atherosclerosis in mice. Although the mechanism still needs to be worked out, it appears that CXCR2 expression on lesion Mphi is essential for these cells to be retained in the lesion.