Objective: We sought to determine the contribution of adipose tissue to the insulin resistance of pregnancy. We also investigated whether hyperosmolar stress (induced by sorbitol) stimulates glucose uptake in human adipose tissue and, if so, whether this effect is altered in pregnancy and gestational diabetes mellitus. Study design: Subcutaneous and omental adipose tissue biopsy specimens were obtained at elective abdominal surgery or cesarean delivery from 16 normal glucose-tolerant pregnant women, 13 pregnant women with gestational diabetes mellitus, and 19 body mass index-matched nonpregnant control subjects. Basal, insulin (100 nmol/L)-, and sorbitol (250 mmol/L)- stimulated glucose uptake levels were measured. Results: Basal and insulin-stimulated glucose uptake into adipose tissue was not impaired in pregnancy or gestational diabetes mellitus compared with control subjects. Hyperosmolarity stimulated glucose uptake in human adipose tissue from the subcutaneous, but not omental depot, and not in adipose tissue from pregnant subjects. Conclusion: There is no significant difference in insulin sensitivity in adipose tissue from pregnant or nonpregnant women; hyperosmolarity stimulates glucose uptake in subcutaneous adipose tissue from nonpregnant women, and adipose tissue from pregnant women is sorbitol resistant. These findings suggest the phosphotidylinositol 3- kinase-independent pathway may have pathophysiologic relevance to glucose uptake in human adipose tissue and may be impaired in pregnancy. Objective: We sought to determine the contribution of adipose tissue to the insulin resistance of pregnancy. We also investigated whether hyperosmolar stress (induced by sorbitol) stimulates glucose uptake in human adipose tissue and, if so, whether this effect is altered in pregnancy and gestational Study design: Subcutaneous and omental adipose tissue biopsy specimens were obtained at elective abdominal surgery or cesarean delivery from 16 normal glucose-tolerant pregnant women, 13 pregnant women with gestational diabetes mellitus, and 19 body mass index-matched nonpregnant control subjects. Basal, insulin (100 nmol / L) -, and sorbitol (250 mmol / L) - stimulated glucose uptake levels were measured. Results: Basal and insulin- stimulated glucose uptake into adipose tissue was not impaired in pregnancy or gestational diabetes mellitus compared with control subjects. Hyperosmolarity stimulated glucose uptake in human adipose tissue from the subcutaneous, but not omental de pot, and not in adipose tissue from pregnant subjects. Conclusion: There is no significant difference in insulin sensitivity in adipose tissue from pregnant or nonpregnant women; hyperosmolarity stimulated glucose uptake in subcutaneous adipose tissue from nonpregnant women, and adipose tissue from pregnant women is sorbitol resistant. These findings suggest the phosphotidylinositol 3-kinase-independent pathway may have pathophysiologic relevance to glucose uptake in human adipose tissue and may be impaired in pregnancy.