Cells need cholesterol to survive, but excess cholesterol is toxic to cells, so cells need to regulate cholesterol homeostasis. Intracellular cholesterol is transported to the high density lipoprotein-apolipoprotein AI, which returns to the liver in reverse cholesterol transport (RCT) route, and ultimately excretes through feces. RCT is not only a physiological process necessary to maintain cellular cholesterol homeostasis, but also has potential atherosclerosis inhibition. Current studies have mainly focused on the initial pathway of cellular cholesterol efflux and the final metabolism of cholesterol in the blood, but little is known about how cholesterol can leave the blood. More and more studies have shown that HDL needs to be transported through lymphatic vessels during RCT to return to liver in which cholesterol is metabolized. Therefore, it is important to better understand the process of HDL flowing from blood to peripheral tissue, to change and promote the removal of intracellular cholesterol in the tissue space and how it is transported through lymphatic vessels. This review focuses on the relationship between lymphatic vessels and RCT, which provides a new strategy for the treatment of atherosclerotic vascular diseases.