Neonates display a significantly impaired ability to concentrate urine. In rats, urinary concentrating ability nearly reaches adult level at weaning (postnatal day 21, P21). Cyclooxygease type 2 (COX2) and prostaglandin production is up-regulated in rat and human kidney in the early postnatal period. We hypothesized that COX-2 activity contributes to impaired concentrating ability and tested the hypothesis in rat pups. Urinary concentrating ability and papillary osmolality was examined after water (maternal) deprivation in control pups, indometacin-treated pups (5 mg/kg) and parecoxib-treated pups (5mg/kg, a selective COX-2-inhibitor) at P14 (12h) and at P21 (24h). At P14, urine osmolality of control rats was 693 ± 165 (n = 9), 646 ± 116 (indometacin, n = 9) and 711 ± 197 (parecoxib, n = 9) mOsm/kg H2O with no significant differences. Papillary osmolality at P14 was 584 ± 105 mOsm/kg (control, n = 6), 574 ± 38 (indometacin, n = 5) and 590 ± 155 mOsm/kg (parecoxib, n = 6). At P21, urinary osmolality after water deprivation was 1661 ± 444 (control, n = 6), 1196 ± 625 (indometacin, n = 7) and 1153 ± 511 mOsm/kg (parecoxib, n = 7) (vehicle treated > parecoxib treated; p < 0.05). Papillary osmolality at P21, after water deprivation was 1134 ± 217 (control, n = 6), 922 ± 720 (indometacin, n = 7) and 1057 ± 246 mOsm/kg (control, n = 7) (vehicle treated > indometacin treated; p < 0.04). Efficient blockade of COX-2 was confirmed by metabolite measurements. Our data show a developmental increase in urinary concentrating ability and papillary interstitial osmolality that was not diminished but rather increased by COX-2 activity.