This review summarizes both the structure and function of IL-1 receptor antagonist (IL-1Ra), and relates our new findings, particularly those obtained in IL-1Ra-deficient mice (IL-1Ra(-/-)), to the role of IL-1Ra in arterial diseases and cholesterol metabolism. IL-1Ra(-/-) mice show an increase in neointima-formation after arterial injury. Heterozygosity in the IL-1Ra gene against the apolipoprotein E-deficient background revealed a role for IL-1 in promoting atherogenic cell signaling and that the larger lesions of IL-1Ra(-/-) mice are enriched in macrophages and depleted of smooth muscle cells. Furthermore, IL-1Ra(-/-) mice developed severe fatty livers and hypercholesteroremia following 20 weeks on a atherogenic diet compared to WT mice. Taken together, these results suggest that IL-1Ra plays important roles in restenosis after angioplasty, the development of atherosclerosis, and the metabolism of cholesterol in vivo.