This study was designed to investigate the effect of curcumin on the expression of thrombospondin-4 (THBS-4) in mouse macrophages treated with oxidized low-density lipoprotein (oxLDL). The mouse macrophage cell line ANA-1 was treated with oxLDL. Cell viability was measured by MTT assay. ANA-1 cells were divided into five groups: control group, model group, 5 μM curcumin group, 15 μM curcumin group and 25 μM curcumin group. The gene and protein expression levels of THBS-4 in each group were determined by real-time quantitative polymerase chain reaction (PCR) and western blotting, respectively. MTT assay showed that curcumin concentrations up to 25 μM and oxLDL concentrations up to 20 μg/ml had no significant cytotoxic effects on macrophages at 24 h. Real-time quantitative PCR revealed that THBS-4 mRNA expression was markedly reduced by stimulation with oxLDL, but subsequently significantly increased by treatment with curcumin. Western blotting confirmed that curcumin (5, 15, and 25 μM) significantly prevented the decrease in THBS-4 expression induced by oxLDL (20 μg/ml) in macrophages. Curcumin prevents the decrease in THBS-4 expression induced by oxLDL, which may represent one of the anti-atherosclerotic mechanisms of curcumin.