The primary function of the gastrointestinal tract is the digestion and absorption of ingested food and water. The gastrointestinal blood circulation is responsible for delivery of the oxygen required for the absorptive and secretory functions of the mucosa and the motor activity of the muscularis. The distribution of absorbed nutrients and water to all the organs of the body is accomplished by way of both the blood and lymph circulations. At rest, the gastrointestinal tract accounts for one-fourth of total body oxygen consumption and cardiac output, and this demand is increased postprandially. Herein, the overall objective is to summarize the physiologic role of the blood and lymph vessels in supporting the overall absorptive, secretory, and motor function of the stomach, small intestine, and colon with an emphasis on the mucosal microcirculation. The major issues to be addressed include: (1) the vasoregulatory mechanisms involved in meeting the enhanced O₂ demand of assimilation of ingested nutrients and (2) the alterations in forces and membrane parameters governing transcapillary fluid exchange, which allow for efficient delivery of nutrients to other organs without compromising mucosal integrity. In addition, two pathologic conditions in which the gastrointestinal microcirculation plays a critical role will be addressed: ischemia/reperfusion (I/R) and portal hypertension (PH).