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Perilipin first was thought only expressed in adipocytes and steroidogenic cells and it was also observed in macrophages and human atherosclerotic plaques in past few years.Perilipin experssion was increased in human atheroma and overexpression perlipin could enhance lipid accumulation in THP-1 cell, which make us consider if perilipin konckout decrease atherosclerosis development.In this study, we show that plin gene inactivation in apolipoprotein E-deficient (ApoE-/-) mice protects the mice against atherosclerosis.Moreover, transplantation of plin-null bone marrow-derived cells effectively attenuated atherosclerosis in LDLR-/-mice, which shows the results connected with macrophages.The macrophage forms foam cells are very important in atherosclerosis.Althought histopathologic analysis of atherosclerotic lesions show there is no difference in macrophages, decifiency of plin in macrophages impairs foam cell formation in vitro which decrease lipid accumulation in macrophages.And we detected no significant difference in lesion composition.In conclusion, plin inactivation in ApoE/ background protects against atherosclerosis and the results is because of impaired fame cell formation.