Macrophage-derived foam cell transformation is considered to be an early change in the formation and development of atherosclerosis (AS). Excessive lipid accumulation in the macrophage-derived foam cell often promotes vascular intimal growth and necrosis, which leads to plaque instability and thrombosis. Recent evidence indicated that Celasrol (CeT) can significantly regulate lipid metabolism, which has potential therapeutic significance in the process of foam cell transformation. In this study, CeT treatment can reduce the accumulation of lipid droplets in lipid-loaded Raw264.7 cell in concentration-dependent manner, and up-regulate the protein expression of ABCA1 and LXRα, the key molecules of cholesterol transport in Raw264.7. In addition, the results showed that knockdown of ABCA1 promoted lipid storage, while CeT reduced intracellular lipid accumulation and up-regulated ABCA1 expression. Moreover, LC3II /I ratio was increased and p62 was decreased after treatment with CeT for 24 h. Besides, the intracellular lipid level was restored following exposure to autophagy inhibitor 3MA. In summary, CeT can reduce intracellular lipid accumulation by up-regulating LXRα / ABCA1 signal and activating autophagy of lipocytes. Therefore, further study about the role of CeT in the transformation of macrophage derived foam cells may be a promising strategy for AS therapy and underlying target for drug intervention.