African Americans are more insulin resistant than Caucasian Americans and this discrepancy cannot be explained by measures of body weight or body composition. The aim of the study was to compare the sensitivity of African Americans and Caucasian Americans to glucocorticoids by measuring glucose and insulin responses to a meal challenge under conditions of placebo and glucocorticoid. A total of 160 healthy or overweight/obese African American and Caucasian American participants completed exercise testing and a liquid meal challenge during separate laboratory visits. Participants were evaluated following treatments with placebo and dexamethasone (4 mg). Main outcome measures were correlation between body composition measures (body mass index, percent body fat, waist circumference) and insulin responses; insulin and glucose responses after a liquid meal challenge; and calculated HOMA. After dexamethasone treatment African Americans were significantly more hyperinsulinemic after a meal as indicated by higher peak insulin (p=0.02) and postprandial insulin areas under the curve (p=0.006) than Caucasians. Additionally, African Americans were more insulin resistant than Caucasian Americans under both placebo and dexamethasone as determined by fasting insulin and HOMA (p=0.05). Waist circumference correlated with post-dexamethasone insulin AUC and HOMA in Caucasian Americans (p<0.05), but none of the body composition measures were predictive of IR for African Americans. African Americans are more sensitive to glucocorticoids (dexamethasone) than Caucasian Americans, as indicated by significantly greater peak insulin and postprandial insulin areas under the curve. The glucocorticoid receptor and its potential interactions with stress may contribute to this ethnic disparity.