Down-regulation of multidrug resistance protein 2 (Mrp2), a major canalicular organic anion transporter, has been reported in various cholestatic models and in patients with cholestasis. In the present study, biliary excretion of taurolithocholate-sulfate and temocaprilat, substrates of Mrp2, was studied in bile duct-ligated rats and in cholestatic rats induced by ethinylestradiol (EE). Biliary excretion of temocaprilat was more markedly decreased in bile duct-ligated rats than that of taurolithocholate-sulfate. In contrast, biliary excretion of both compounds were similarly inhibited in EE-treated rat. Such difference of the degree of inhibition may have been caused by the different degree of the inhibition of unknown canalicular transporters other than Mrp2 in bile duct-ligated rats.