We have previously shown that expression of renal organic anion transporters Oat1 and Oat3 is diminished by prostaglandin E2 (PGE2) and that both transporters are down regulated after renal ischemia. As PGE2 is increased after renal ischemia and is generated by cyclooxygenases (COX), we investigated the effect of the COX-inhibitor indomethacin on expression of Oat1/3 after ischemic acute kidney injury (iAKI). iAKI was induced in rats by bilateral clamping of renal arteries for 45 min. Indomethacin (1mg/kg) was given intraperitoneally as soon as reperfusion started. Sham treated animals served as controls. Oat1/3 were determined by qPCR and western blot. PGE2 in blood and urine was measured by ELISA. Invasion of monocytes/macrophages was determined. Glomerular filtration rate and renal plasma flow was determined. All parameters were detected 24 h after ischemia. PAH net secretion, as well as clearance and secretion of PGE2 were calculated. In clamped animals indomethacin restored expression of Oat1/3, as well as PAH net secretion, PGE2 clearance or PGE2 secretion. Additionally, indomethacin substantially improved kidney function as measured by glomerular filtration and PAH clearance. Indomethacin did not affect ischemia induced invasion of monocytes/macrophages. In conclusion our study indicates that low dose indomethacin applied after ischemia prevents ischemia induced down regulation of Oat1/3 during reperfusion and has a substantial protective effect on kidney function after iAKI. The beneficial effect of low dose indomethacin on renal outcome is likely due to an effect different from inhibition of inflammation. In accordance to the decreased PAH net secretion, renal excretion of an endogenous organic anion (PGE2) is also impaired after ischemia and reperfusion.