The corpus luteum (CL) undergoes drastic changes in its function and structure during the estrous cycle. To secrete a sufficient amount of progesterone (P4) to ensure the occurrence of pregnancy in a cow with a body weight greater than 500 kg, the bovine CL weighs 5-8 g which is 2-3 thousand times heavier than rat CL. If pregnancy does not occur successfully, rapid luteolysis is caused by prostaglandin F2α (PGF2α) that is released from the endometrium around days 17-19 of the estrous cycle in the cow. Thus, it is clear that the bovine CL lifespan is controlled by well-coordinated mechanisms. As the CL matures, the steroidogenic cells establish contact with many capillary vessels, so that the CL is composed of a large number of vascular endothelial cells that can account for up to 50% of all cells in the bovine CL. Also, luteal endothelial cells secrete several vasoactive substances such as PGF2α, nitric oxide, endothelin-1 and angiotensin II that regulate blood flow as well as P4 secretion in an autocrine/paracrine manner within the CL. Therefore, blood vessels and endothelial cells within the CL have an essential role in luteal function in the cow, suggesting that the study of vasoactive molecules from the CL is of great importance to give an insight into systems which regulate luteolysis locally. In the present review, we describe novel concepts on the luteolytic mechanisms in the cow, with emphasis on luteal blood flow and vasoactive molecules.