Rat offspring prenatally exposed to alcohol display features of metabolic syndrome characterized by a low birth weight, catch-up growth, dyslipidemia, and insulin resistant diabetes with increased gluconeogenesis, during adult life. Gluconeogenesis is partly regulated by cyclic AMP- and glucocorticoid-dependent mechanisms. Glucocorticoid action at the receptor level depends on its circulating concentrations and is amplified at the prereceptor level by 11-hydroxysteroid dehydrogenase type 1 (11-HSD1), which regenerates active glucocorticoids from inactive forms. To determine if 11-HSD1 is dysregulated in this rat model, we examined the expression and enzyme activity of 11-HSD1 and its regulator enzyme hexose-6-phosphate dehydrogenase (H6PD) in the liver of postnatal day-7 (neonatal) and 3-months (adult) old rat offspring prenatally exposed to alcohol. Measurements of 11-HSD1 and H6PD were also performed in the omental fat of adult rat offspring. In both neonatal and adult rats, prenatal alcohol exposure resulted in increased tissue corticosterone concentrations, increased expression and oxoreductase activity of 11-HSD1 and a parallel increase of H6PD expression. The data suggest that due to both transcriptional and post-transcriptional dysregulations, rats exposed to alcohol early in life have increased 11-HSD1 activity, which may explain insulin resistant diabetes in these animals later in life.