Low birth weight in humans predisposes to obesity, cardiovascular diseases, and type 2 diabetes in adult life. Alcohol exposure during pregnancy has been associated with fetal growth restriction. We investigated the effects of prenatal exposure to alcohol on glucose metabolism later in the offspring. Female Sprague Dawley rats were given ethanol (ETOH), 4 g/kg/day by gavage throughout pregnancy. Compared with controls, newborn ETOH rats had decreased body size (5.1 [plusmn] 0.1 v 6.3 [plusmn] 0.1 g, P [lt ] .001), plasma insulin (0.44 [plusmn] 0.4 v 0.67 [plusmn] 0.1 ng/mL, P [lt ] .05), and leptin mRNA (P [lt ] .05), but they had normal [beta ]-cell mass and elevated adipose resistin mRNA and plasma glucose (5.0 [plusmn] 0.5 v 3.6 [plusmn] 0.3 mmol/L, P [lt ] .01). Food intake was decreased in ETOH rats during the fourth week of life, and body weight remained decreased compared with controls until a catch-up growth occurred by 7 weeks of life. At 13 weeks of age, body weight and [beta ]-cell mass of ETOH offspring were normal, but plasma glucose and insulin after a glucose challenge were increased compared with controls (P [lt ] .05). Adipose leptin and hypothalamic Ob-R mRNA were not different from controls, but resistin was increased (P [lt ] .05), and muscle GLUT4 content was decreased (P [lt ] .05) in ETOH offspring compared with controls. The data suggest that prenatal alcohol exposure impairs glucose tolerance in the offspring by both inducing insulin resistance and [beta ]-cell dysfunction. The prevailing mechanism in 3-month-old rat offspring appears to be insulin resistance, manifested by glucose intolerance and decreased GLUT4 despite hyperinsulinemia.