Aim To investigate the effect of diosgenin （Dgn） on ABCA1 expression and cholesterol efflux in THP-1 derived macrophage. Methods ABCA1 expression was detected by Western blot. Cholesterol efflux was detected with liquid scintillator intracellular total cholesterol （TC）, free cholesterol （FC） and cholesterol ester （CE） were determined with HPLC and intracellular lipid droplet was stained with oil red O in THP-1-derived macrophage treated with Dgn, alone or in combination with ABCA1 siRNA. Results Dgn upregulated macrophage ABCA1 expression in dose-dependent manner. Dgn obviously facilitated macrophage cholesterol efflux, resulting in a decrease in intracellular level of TC, FC, CE and lipid droplet, and the foam cell formation. However, the action of Dgn-facilitating cholesterol efflux was almost entirely abrogated in THP-1 derived macrophage coincubated with ABCA1 siRNA, causing excessive lipid accumulation and increase formation of foam cells. Conclusion Dgn promotes macrophage ABCA1 expression and cholesterol efflux, which suppresses intracellular lipid accumulation and foam cell formation.