Apelin was isolated and characterized as an endogenous ligand for a G protein-coupled receptor, APJ. Human apelin gene encodes a pre-proprotein of 77 aa residues. After cleavage of the signal peptide, the proprotein of 55 aa residues generates several active fragments, including apelin 36, apelin 17, and apelin 13. Apelin 13 is highly active and responsible for the APJ binding and biological activities of mature apelin. In mammalians, expression of apelin mRNA is seen in cardiovascular, digestive, urinary, and central nervous systems. Apelin induces a very wide range of biological effects, such as hypotensive effect through nitric oxide (NO) release, angiogenesis, and stimulation of cardiac contractility, water intake, and diuretic effect, as well as inhibiting HIV infection. Apelin-KO mice show impaired retinal vascularization and ocular development. The apelin-induced hypotensive effect is abolished in APJ-deficient mice.