Objective: Several reports describe the role of interleukin (IL)-17 in the development of atherosclerosis; however, its precise role remains controversial. We generated double-deficient mice for apolipoprotein E (apoE) and IL-17 (apoE(-/-)IL-17(-/-) mice) and investigated the effect of IL-17 deficiency on vascular inflammation and atherosclerosis. Methods and results: Atherosclerotic plaque areas in apoE(-/-)IL-17(-/-) mice fed a Western diet (WD) were significantly reduced compared with those in apoE(-/-) mice. No significant differences in plasma lipid profiles were observed between apoE(-/-) and apoE(-/-)IL-17(-/-) mice. The number of infiltrated macrophages in the plaques was significantly decreased in WD-fed apoE(-/-)IL-17(-/-) mice compared with WD-fed apoE(-/-) mice, whereas vascular smooth muscle cell content was not altered by IL-17 deficiency. Expression of inflammatory cytokines (MCP-1, IL-1 beta, IL-6, IFN-gamma, and IL-12 p40) and scavenger receptors (Msr-1, Scarb1, and Olr1) in the plaques was inhibited in WD-fed apoE(-/-)IL-17(-/-) mice. Furthermore, expression of inducible nitric oxide (M1 marker) and arginase-1 (M2 marker) was inhibited in WD-fed apoE(-/-)IL-17(-/-) mice. Conclusion: Our results indicate that IL-17 deficiency reduces vascular inflammation and atherosclerosis and that modulation of IL-17 could be a potential target for prevention and treatment of atherosclerosis. (C) 2012 Elsevier Inc. All rights reserved.