As an important chain-breaking antioxidant, the role of Vitamin E has attracted attentions from all over the world. Alpha-Tocopherol and gamma-tocopherol are two of the eight different forms of vitamin E. The dietary intake of gamma-tocopherol is generally higher than that of alpha-tocopherol. However, the levels of alpha-tocopherol in human blood have consistently been shown to be higher than those of gamma-tocopherol. This could be due, in part, to a differential cellular uptake of the two tocopherol forms. We sought to resolve this question by studying the uptake and depletion of both alpha-tocopherol and gamma-tocopherol in RAW 264.7 macrophages. The results indicate that a faster uptake and depletion of gamma-tocopherol compared with alpha-tocopherol. The presence of gamma-tocopherol can promote the uptake of alpha-tocopherol by macrophages. The metabolism of alpha-tocopherol was faster than gamma-tocopherol. These results implied the existence of a hypothetical transport protein, which can preferentially select gamma-tocopherol over alpha-tocopherol. The affinity of this transport protein for alpha-tocopherol could be increased by the presence of gamma-tocopherol.