In order to explore the effects of pomegranate peel polyphenols (PPPs) on SR-B1 protein expression and cholesterol efflux, in this study, Raw264.7 macrophages derived from foam cells were used as the model to illuminate the effects of PPPs on cholesterol efflux mediated by HDL. Western blot method was used to analyze the expression of scavenger receptor B1 (SR-B1), acyl-coenzyme A1: cholesterol acyltransferase (ACAT1) and cholesteryl ester hydrolase (nCEH). Further, the activity changes of ACAT1 and nCEH were revealed. The results showed that PPPs promoted the HDL-mediated cholesterol efflux and up-regulated the expression of SR-B1 significantly (P＜0.05). In addition, the PPPs had no significant effects on nCEH and ACAT1 protein expression (P＞0.05), but could significantly reduce the enzyme activity of ACAT1 and increase that of nCEH (P＜0.05), which facilitated the transformation and outflow of intracellular cholesterol esters to free cholesterol.