To investigate the role of TWEAK/Fn14 axis on diabetic-accelerated atherosclerosis, we studied the development of atherosclerotic plaques in Tnfsf12+/+ApoE−/−, Tnfsf12−/−ApoE−/−, and anti-TWEAK- or IgG-treated ApoE−/− in streptozotocin-induced diabetic ApoE deficient mice. This evidence concerns the gene APOE and atherosclerosis.