CLA reduces intracellular cholesterol content of human macrophage derived foam cells. HBPMCs-derived M-CSF stimulated macrophages, following treatment with c-9,t-11-CLA, t-10,c-12-CLA, CLA blend (80:20 c-9,t-11:t-10,c-12), OA, LA or TROG were ox-LDL loaded for 4 hours and cholesterol content measured by enzymatic assay. CLA blend and c-9,t-11-CLA significantly decrease the levels of both total cholesterol (TC) and free cholesterol (FC), whilst, t-10,c-12-CLA and OA decrease the FC fraction. The effect of CLA on cholesterol trafficking is regulated by a dual mechanism involving PPARγ/LXRα-dependent. Data are expressed as % of TC or FC content over vehicle control, where *p < 0.05, **p < 0.01 and are the mean of three independent experiments.