Atherosclerosis is a chronic vascular inflammation caused by lipid deposition. The onset and progression of atherosclerotic lesions are closely related to the disturbance of cellular cholesterol homeostasis. ATP-binding cassette transporter A1 (ABCA1) mediates active cholesterol efflux to apolipoprotein AⅠ, preβ high density lipoprotein (HDL), and HDL₃. The impairment of this cholesterol efflux pathway leads to the intracellular accumulation of cholesterol esters. Importantly, loss-of-function mutations of ABCA1 influence the growth of atherosclerotic plaques and the incidence of coronary heart diseases. Recent studies using transgenic animals have shown that effects of ABCA1 on atherosclerosis are tissue/cell-specific. This paper focuses on the role of tissue/cell-specific ABCA1 in atherosclerosis and underlying mechanisms after briefly introducing reverse cholesterol transport and atherosclerosis.