It has been well known that foam cells formation is one of the hallmarks of early atherosclerosis. Reverse cholesterol transport (RCT) pathway can inhibit the foam cells formation. ATP-binding cassette transporter G1 (ABCG1) plays a crucial role in RCT and anti-atherosclerosis, which mediates the efflux of cholesterol to HDL. Liver X receptor alpha (LXRα) can stimulate cholesterol efflux through ABCG1. It has been well known that adiponectin has cardiovascular protection. In this study, we attempted to clarify the effect of adiponectin on expression of ABCG1, and explored the role of LXRα in the regulation of ABCG1 in RAW 264.7 macrophages. The expression of ABCG1 and LXRα were examined by Real-time quantitative PCR and Western blot analyses. Cellar cholesterol efflux from THP-1 macrophage was analyzed by liquid scintillation counting assays. Our results showed that adiponectin increased ABCG1 expression at both the mRNA and protein levels in a dose-dependent and time-dependent manner. Consequently, adiponectin promoted cholesterol efflux in RAW 264.7 macrophages. Moreover, adiponectin up-regulated the expression of LXRα in a dose-dependent and time-dependent manner in RAW 264.7 macrophages. LXRα small interfering RNA completely abolished the promotion effects of adiponectin. In summary, adiponectin up-regulates ABCG1 expression via the LXRα pathway in RAW 264.7 macrophages.