To determine whether sulfatide liposomes can cross the blood-brain barrier (BBB) with or without osmotic treatment by mannitol, we administered liposomes through the internal carotid artery in rats. Sulfatide liposomes could pass the BBB with osmotic treatment, but not without osmotic treatment. Therefore, we propose that the combination method of administration of the reticuloendothelial-system avoiding liposomes with osmotic treatment can be useful for treatment of various kinds of brain diseases.