Clinical and animal studies indicate that intrauterine growth restriction (IUGR) following uteroplacental insufficiency (UPI) reduces nephron number and predisposes towards renal insufficiency early in life and increased risk of adult onset hypertension. In this study we hypothesized that the inducible enzyme cyclooxygenase-2 (COX-2), a pivotal protein in nephrogenesis, constitutes a mechanism through which UPI and subsequent glucocorticoid overexposure can decrease nephron number. We further hypothesized that UPI down regulates the key enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11 -HSD2), which converts corticosterone to inert 11-dehydrocorticosterone, thereby protecting both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) from the actions of corticosterone. Following bilateral uterine ligation on the pregnant rat, UPI significantly decreased renal COX-2, 11-HSD2 and GR mRNA and protein levels, but up regulated expression of MR at birth. At day of life 21, 11-HSD2, GR and also MR mRNA and protein levels were down regulated. UPI did not affect blood pressures (BP) at day 21 of life, but significantly increased systolic BP in both genders at day 140. We conclude that in our animal model, UPI decreases fetal COX-2 expression during a period of active nephrogenesis in the IUGR rat, which is also characterized by decreased nephron number and adult onset hypertension.