Plasma high density lipoprotein (HDL)-cholesterol levels are inversely correlated with the incidence of cardiovascular diseases. HDL is mainly assembled in the liver through the ATP-binding cassette transporter (ABCA1) pathway. In humans, plasma HDL-cholesterol levels are positively correlated with plasma adiponectin (APN) concentrations. Recently, we reported that APN enhanced apolipoprotein A-I (apoA-I) secretion and ABCA1 expression in HepG2 cells. In the present study, we investigated HDL assembly in APN-knockout (KO) mice. The apoA-I protein levels in plasma and liver were reduced in APN-KO mice compared with wild-type-mice. The ABCA1 expression in liver was also decreased in APN-KO mice. APN deficiency might cause the impaired HDL assembly by decreasing ABCA1 expression and apoA-I synthesis in the liver.