Hemoglobin-vesicles (HbV) or liposome-encapsulated hemoglobin (LEH) are artificial oxygen carriers that mimic the cellular structure of RBCs. In contrast to other liposomal products containing antifungal or anticancer drugs, one injection of HbV in place of a blood transfusion is estimated as equivalent to a massive dose, such as several hundred milliliters or a few liters of normal blood contents. The fluid must therefore contain a sufficient amount of Hb, the binding site of oxygen, to carry oxygen like blood. Encapsulation of Hb can shield various toxic effects of molecular Hbs. On the other hand, the liposomal structure, surface property, and the balance between the stability for storage and blood circulation and instability for the prompt degradation in the reticuloendothelial system must be considered to establish an optimal transfusion alternative.