Release of bilateral ureteral obstruction (BUO) is associated with reduced expression of renal aquaporins (AQPs), polyuria and impairment of urinary concentration capacity. Recently, we demonstrated that 24hBUO is associated with increased cyclooxygenase-2 (COX-2) expression in inner medulla (IM) and that selective COX-2 inhibition prevents downregulation of AQP2. In the present study, we tested the hypothesis that COX-2 activity increases in the post-obstructive phase and that this contributes to polyuria and impaired urinary concentration capacity. We examined the effect of the selective COX-2 inhibitor parecoxib (5 mg/kg/day via osmotic minipumps) on renal functions and protein abundance of AQP2 and -3 as well as on NKCC2 and Na-K-ATPase 3 days after release of BUO. Three days after release of BUO, rats exhibited polyuria, dehydration and decreased urinary and IM tissue osmolality. There were inverse changes of the 2 COX isoforms in IM. COX-2 mRNA, protein and activity increased, while COX-1 mRNA and protein decreased. Administration of parecoxib reduced urine output 1 day after release of BUO but sodium excretion and GFR were unchanged. Parecoxib normalized urinary PGE2 and PGI2 excretion and attenuated downregulation of AQP2 and AQP3 while pAQP2 and NKCC2 remained suppressed. Parecoxib treatment did not improve urinary concentrating capacity in response to 24h water deprivation. We conclude that decreased NKCC2 and collapse of the inner medullary osmotic gradient together with suppressed pAQP-2 are likely causes for the impaired urinary concentrating capacity and that COX-2 activity is not likely to mediate these changes in the chronic post-obstructive phase after ureteral obstruction.