ABSTRACTThe normal function of skeletal muscle requires that a continuous supply of oxygen be provided by the cardiovascular system. This article reviews the development of our understanding of the role of microvascular architecture on the oxygen transport system, with emphasis on direct microcirculatory observations and mathematical modeling dating from the work of August Krogh to present studies. The contributions of the various elements of the vascular network (i.e., arterioles, capillaries, and venules) and microvascular hemodynamics to oxygen exchange are discussed. Oxygen moves through the microvascular network by convection, almost all of it being reversibly bound to the hemoglobin within red blood cells. Thus, the flow properties and distribution of the red cells within the network can play a significant role in oxygen transport. Because the walls of all the vessels in the microcirculation appear to be permeable to oxygen, it continuously diffuses between the blood and the interstitium, the direction depending on the oxygen partial pressure difference. Because of the high permeability of the vascular wall to oxygen, the complex spatial relationships among the various microvessels lead to correspondingly complex diffusive interactions among them. The proximity of capillaries, arterioles, and venules, along with the anastomotic connections and tortuosity of capillaries, provides the “complex spatial relationships” that lead to diffusive interactions between neighboring capillaries, between capillaries and nearby arterioles and venules, and between paired arterioles and venules. Although there are a number of outstanding problems regarding our understanding of oxygen transport at the microcirculatory level, the most interesting and significant of these has to do with the adjustments that are made in the transition from the resting state to that of sustained aerobic exerc