Results of numerous studies using varied experimental approaches have established a role for macrophage-derived apolipoprotein E in modulating cholesterol balance in the arterial wall, thereby potentially modulating progression or regression of the vessel wall atherosclerotic lesion. Macrophage-derived apolipoprotein E could also act on the vessel wall by modulating the aggregability of platelets and the proliferation of lymphocytes. In addition, macrophage-derived apolipoprotein E interacts with extracellular matrix and such interactions could influence the retention of lipoproteins in the vessel wall, the bioavailability of cytokines and growth factors sequestered in the extracellular matrix and the regulation of arterial smooth muscle cell growth by matrix components.