Abstract The uptake of oxidized low density lipoprotein (oxLDL) via scavenger receptors transforms macrophages into foam cells, which are a hallmark of atherosclerosis. OxLDL markedly increases the expression of the CD36 scavenger receptor. Here, we investigated whether curcumin modulate CD36 expression in oxLDL-treated RAW 264.7 murine macrophages. Our results showed that curcumin dramatically inhibits CD36 expression and foam cell formation. Furthermore, oxLDL-induced expression and activity of peroxisome proliferator-activated receptor-gamma (PPAR-γ), which is involved in CD36 expression, is also blocked in curcumin-treated cells. OxLDL activates the mitogen-activated protein kinase (MAPK) signaling transduction pathway, and p38 MAPK is associated with oxLDL-induced CD36 and PPAR-γ expression. Overexpression of dominant negative p38 MAPK blocks oxLDL-induced CD36 and PPAR-γ expression. Furthermore, curcumin markedly inhibits p38 MAPK phosphorylation. Taken together, our results suggest that curcumin modulates oxLDL-induced CD36 expression and foam cell formation via the inhibition of p38 MAPK phosphorylation in RAW 264.7 murine macrophages.