We studied glucose metabolic adaptations in the intrauterine growth restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), that is altered when there is imbalance between glucose production and utilization, was studied during glucose tolerance test (GTT) in 2 day old (n=8), 2 month-old (n=22), and 15 month-old (n=22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n=5 per age), postnatal (SM/CP, n=6), or pre- and postnatal (SM/SP, n=6) nutrient restriction were compared to age-matched controls (CM/CP, n=5). At 2d, IUGR pups (SP) were smaller and glucose intolerant, had increased hepatic glucose production and increased glucose disposal (p<0.01) compared to control (CP). At 2 m the GTT, the glucose clearance and GFC did not change. However, a decline in hepatic glucose-6-phosphatase (p<0.05) and fructose 1,6, bisphosphatase (p<0.05) enzyme activities in the IUGR offspring was detected. At 15 m prenatal nutrient restriction (CM/SP) resulted in greater weight gain (p<0.01) and hyperinsulinemia (p<0.001) compared to postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, p < 0.01) and postnatal calorie (SM/CP, p < 0.03) and growth restricted offspring. The IUGR offspring with pre- and post natal nutrient restriction (SM/SP) were smaller, hypoinsulinemic (p<0.03), hypoleptinemic (p<0.03), with no change in GTT, hepatic glucose production, futile cycling or glucose clearance. We conclude that there is pre and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype specific manner.