Activators of PPARα have been demonstrated to inhibit atherosclerosis development due to lipid lowering in plasma and direct protective effects on the vasculature. Because dietary oxidised fats (OF) have strong PPARα-activating and lipid-lowering properties, we hypothesised that dietary OF has also an inhibitory influence on atherosclerosis development. To verify our hypothesis, we investigated the effect of feeding diets containing an OF (a 92 : 8 mixture of heated (170°C, 48 h) hydrogenated palm fat and fresh sunflower oil) compared with a fresh fat (fresh hydrogenated palm fat) on the development of atherosclerotic lesions in LDL receptor-deficient (LDLR− / − ) mice. We observed that a dietary OF caused a strong up-regulation of PPARα-regulated genes in the liver and a marked reduction in plasma concentrations of cholesterol and TAG (P < 0·05). Cross-sectional lesion area and the lipids and collagen levels in the aortic root were approximately 40–50 % lower in mice fed diets containing OF than in those fed diets containing fresh fat (P < 0·05). Immunohistochemical analysis of aortic root sections revealed an about 8-fold increased expression of PPARα and a markedly reduced expression of the proinflammatory vascular cell adhesion molecule-1 and smooth muscle cell (SMC)-specific marker α-actin in LDLR− / − mice fed OF (P < 0·05). We postulate that OF exert anti-atherogenic effects by activation of PPARα both in the liver, which contributes to lipid lowering in plasma, and in the vasculature, which inhibits pro-atherogenic events such as monocyte recruitment and SMC proliferation and migration.