The relative benefit of replacing saturated fatty acid with linoleic acids is still being debated because a linoleic acid-enriched diet increases oxidative and inflammatory stresses, although it is associated with a reduction in serum cholesterol levels. The present study was conducted to evaluate the effect of dietary supplementation of linoleic acid-rich (HL) fat, compared with a saturated fatty acid-rich (SF) fat on atherosclerotic lesion areas, serum and liver cholesterol levels, oxidative stress (urinary isoprostanes and serum malondialdehayde) and inflammatory stress (expression of aortic monocyte chemoattractant protein-1; MCP-1) in apo E-deficient mice. Male and female apo E-deficient mice (8 weeks old; seven to eight per group) were fed an AIN-76-based diet containing SF fat (50 g palm oil and 50 g lard/kg) or HL fat (100 g high-linoleic safflower-seed oil/kg) for 9 weeks. Compared with the SF diet, the HL diet lowered atherosclerosis (P<0·05). It reduced serum total cholesterol levels (P<0·05), increased HDL-cholesterol levels (P<0·05) and lowered liver esterified cholesterol levels (P<0·01). The HL diet-fed mice showed increased expression of MCP-1 mRNA (P<0·05), serum levels of malondialdehayde (P<0·05) and urinary excretion of 2,3-dinor-5,6-dihydro-8-iso-prostaglandin F2α; P<0·05). These results suggest that having biomarkers in vivo for oxidative stress and inflammatory status of endothelial cells does not necessarily indicate predisposition to an increased lesion area in the aortic root in apo E-deficient mice fed an HL or SF diet.