Intake of western diet (WD) high in saturated fat and cholesterol causes formation of foamy monocytes (FMs; monocytes containing intracellular lipid droplets) in the circulation, which contribute to atherogenesis, in apoE-/- mice. It remains to be determined which diet component, fat or cholesterol, is more important in inducing FM formation. Mediterranean-type diet (MedD) high in monounsaturated fat (MUF) protects against atherosclerotic events. It is unknown whether MedD affects FM formation. To address these questions, 4 groups of apoE-/- mice were randomly assigned to the following diets: 1) WD (21% w/w milkfat containing 13.3% saturated fat and 5.9% MUF; 0.2% w/w cholesterol); 2) high-fat low-cholesterol diet (HFD, 21% milkfat; 0.05% cholesterol); 3) high-cholesterol low-fat diet (HCD, 5% milkfat; 0.2% cholesterol); 4) MedD with high cholesterol (21% fat containing 2.6% saturated fat and 13.4% MUF from 15% extra-virgin olive oil, 3% walnut fat, 1.5% almond fat and 1.5% hazelnut fat; 0.2% cholesterol). FMs and phenotypes were examined by flow cytometry. Calorie intake and weight changes were not different among the 4 groups of mice. At 1 week on diets, mice on WD or HCD, but not mice on HFD, had abundant FMs in the circulation (Table). Compared to mice on WD or HCD, mice on MedD had lower proportions of FMs and lower side scatter (SSC) values, indicating less lipid, in FMs. Mean fluorescence intensity of CD36, a scavenger receptor, tended to be lower on FMs in mice on MedD than in mice on WD. At 8 weeks, mice on HFD also had abundant FMs, which were, however, still lower than those in mice on WD. Compared to those in mice on WD, the percentage and SSC values of FMs remained lower in mice on MedD for 8 weeks (Table). In summary, high cholesterol appears to be the major dietary component that induces early FM formation in apoE-/- mice while persistent intake of high saturated fat also induces FM formation. Fewer FMs in mice on MedD than on WD or HCD suggests that MUF in MedD may inhibit FM formation.