High-density lipoprotein (HDL) has significant anti-atherogenic properties, whereas the underlying mechanisms are complex and have not been completely elucidated. Adipocytes produce a variety of adipokines with cardiovascular effects. The dysregulated secretion of adipokines by adipocytes may contribute to the increased risk of atherosclerosis associated with obesity. Clinical evidences indicate that higher plasma HDL-C levels are associated with a favourable adipokines secretion profile, suggesting that HDL might improve the dysregulated adipokines secretion. HDL may diminish lipid accumulation in adipocytes through phosphorylation of PPARgamma and inhibition of aP2 expression, which possibly account for the favourable effects of HDL on adipokines secretion. Therefore, we hypothesize that HDL might exert several beneficial effects on adipocytes, which may relate to its anti-atherogenic properties.