Aim To investigate the effect and mechanism of probucol on macrophages reverse cholesterol transport in vivo, we quantitated the ³H-contents in feces of mice after 48 hours intraperitoneally injected macrophages, which were labeled with ³H cholesterol. And the gene and protein expression of SR-BⅠ,CYP7α,ABCG5 in liver and ABCG5 in intestine were evaluated. Methods 32 male C57BL/6 mice were randomly divided into four groups and treated with either vehicle or different dosage （0.1%, 0.5%, 1.0% W/W） of probucol respectively for 4 weeks, Then In vivo ³H-cholesterol-labeled and cholesterol-loaded macrophages were injected intraperitoneally into the mice. The appearance of ³H-tracer in feces as free cholesterol or bile acids were monitored 48 hours later. RNA and membrane protein of the liver and intestine were extracted and the gene and protein expression of SR-BⅠ,CYP7α,ABCG5 in liver and ABCG5 in intestine were quantified with RT-PCR and Western-blot respectively. Results The fecal total ³H-cholesterol levels were dose-dependently and significantly higher than those in control group, but there were no significant difference between 0.5% and 1.0% probucol groups. The mRNA expression of liver CYP7A1 were dose-dependently up-regulated in mice treated with probucol compared with those in the control group The mRNA expression and the protein expression of liver and intestine ABCG5 dose-dependently increased also in mice treated with probucol. No significant difference exists between 0.5% and 1.0% probucol groups. The SR-BⅠ mRNA and protein levels of the liver in mice treated with probucol did not change significantly compared with control mice. Conclusions Probucol dose-dependently promoted macrophages RCT in vivo in mice. The possible mechanism was that probucol up regulated the expression of liver CYP7A1 and ABCG5 in liver and intestine.