Increased glucose requirements of the gravid uterus during late pregnancy and even greater requirements of the lactating mammary glands necessitate major adjustments in glucose production and utilization in maternal liver, adipose tissue, skeletal muscle, and other tissues. In ruminants, which at all times rely principally on hepatic gluconeogenesis for their glucose supply, hepatic glucose synthesis during late pregnancy and early lactation is increased to accommodate uterine or mammary demands even when the supply of dietary substrate is inadequate. At the same time, glucose utilization by adipose tissue and muscle is reduced. In pregnant animals, these responses are exaggerated by moderate undernutrition and are mediated by reduced tissue sensitivity and responsiveness to insulin, associated with decreased tissue expression of the insulin-responsive facilitative glucose transporter, GLUT4. Peripheral tissue responses to insulin remain severely attenuated during early lactation but recover as the animal progresses through mid lactation. Specific homeorhetic effectors of decreased insulin-mediated glucose metabolism during late pregnancy have yet to be conclusively identified. In contrast, somatotropin is almost certainly a predominant homeorhetic influence during lactation because its exogenous administration causes specific changes in glucose metabolism (and many other functions) of various nonmammary tissues which faithfully mimic normal adaptations to early lactation.