Atherosclerosis is considered as a chronic inflammatory disease that involves multiple cell types and factors. The outside layer of the vessels plays a vital role during pathological development. Under pathological conditions such as obesity and inflammation, perivascular adipose tissue (PVAT) will release adipokines and inflammatory factors through adipocyte phenotype transformation and regulate various inflammatory cells. PVAT regulates the immune response of blood vessels in an “outside-inside” manner and further regulates atherosclerosis. Intervention of PVAT may be a new strategy for prevention and treatment of atherosclerosis.