BACKGROUND Nonsteroidal anti-inflammatory drugs act by inhibiting the rate-limiting enzymes cyclooxygenase-1 (Cox-1) and cyclooxygenase-2 (Cox-2), which are important in prostanoid formation. The aim of this experimental study was to examine the effects of selective Cox-2 inhibitor, rofecoxib, with or without furosemide, on urine and serum electrolytes, creatinine clearance, plasma renin activity (PRA), and Cox-2 expression in the renal cortex. METHODS Forty male Wistar albino rats were randomized into four groups, group 1, group 2, group 3, and group 4, and were treated with placebo, furosemide (20 mg/kg), rofecoxib (10 mg/kg) plus furosemide (12 mg/kg), and rofecoxib (10 mg/kg), respectively, and followed for 7 days. Body weights were measured daily. Urine osmolality and volume, and serum and urinary creatinine, sodium (Na(+)), and potassium (K(+)) were measured. Renal cortical Cox-2 protein expression was examined by immunohistochemical method. RESULTS Compared with groups 1 and 3, body weights were significantly reduced in groups 2 and 4 (16.2 and 19.8 g, respectively; P < 0.05 for all). Urine volume in group 2 increased significantly compared with groups 1, 3, and 4 (P < 0.001, P < 0.008, and P < 0.004, respectively). Urine osmolality in group 2 decreased significantly compared with groups 1 and 3 (P < 0.05 for all). Blood urea nitrogen, serum creatinine and sodium, creatinine clearance, and 24-h urine Na(+) and K(+) levels were similar in all groups. Serum K(+) level was lowest in group 2, and there was a statistically significant difference between groups 2 and 4 (P < 0.05). Plasma renin activity was similar in all groups (P > 0.05). Renal cortical Cox-2 protein expression was lowest in group 1 and was significantly different from the other groups (P < 0.01 for all). The relationship between Cox-2 expression and plasma renin activity was not significant in any group (P > 0.05, r(2):0.05). CONCLUSIONS Rofecoxib neutralized the diuretic effect of furosemide in rats treated with a combination of furosemide and rofecoxib. Renal cortical Cox-2 protein expressions due to furosemide and rofecoxib with or without furosemide were similar and significantly increased compared with controls. Renal failure due to rofecoxib did not developed in any rat, but selective Cox-2 inhibitor, rofecoxib, might have similar renal effects as nonselective nonsteroidal drugs for blunting the diuretic effect of furosemide.