Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) catalyzes the formation of cholesteryl esters (CE) and plays a significant role in formation of macrophage-derived foam cells in atherosclerotic lesions. Adiponectin was reported to play an anti-atherogenic role by inhibiting class A scavenger receptor (SR-A) expression in human macrophages. To further clarify its additional property, we examined its effect on ACAT-1 expression using human macrophages. Immunoblot analyses revealed a significant reduction of ACAT-1 protein by a low concentration (1μg/ml) of adiponectin. The ACAT activity was also decreased in parallel by adiponectin. Northern blot analyses revealed that all four ACAT-1 mRNA transcripts (2.8, 3.6, 4.3, and 7.0kb) were decreased almost equally by adiponectin. Furthermore, acetyl-LDL-induced CE-accumulation in these macrophages was reduced significantly by this adipocytokine. These results demonstrate the inhibitory effect of adiponectin on ACAT-1 expression, suggesting that adiponectin may play an anti-atherogenic role by down-regulating the expression of ACAT-1 as well as SR-A in human macrophages.