It is known that manganese dipyridoxal diphosphate (Mn-DPDP) causes persisting liver enhancement in cholestatic rats, that free Mn ++ plus bilirubin induces intrahepatic cholestasis, and that free Mn ++ is released in vivo after Mn-DPDP injection. Hence, there is a concern about potential secondary intrahepatic cholestasis in patients who have biliary obstruction. In this study, we further investigated this issue.Removable total biliary obstruction (RTBO) was induced in 12 rats. Six of them (group A) received Mn-DPDP (25 μmol/kg). The others (group B) served as control animals. The data from serial magnetic resonance imaging and serum bilirubin tests were compared.Without Mn-DPDP, a minimal increase of the liver intensity was observed in both groups because of cholestasis. In group A, the intensity of the liver was strongly enhanced with Mn-DPDP but normalized within 48 hr after removal of the obstruction. In both groups, total bilirubin levels increased up to 131.67 μmol/l 2 days after RTBO but rapidly decreased within 4 hr and almost normalized within 24 hr after removal of the obstruction, suggesting a lack of Mn-DPDP influence on the bilirubin level.We found that Mn-DPDP did not cause secondary intrahepatic cholestasis. Retained Mn ++ is likely eliminated after restoration of bile flow. These results indicate that Mn-DPDP can be used in patients who have obstructuve jaundice as long as it is followed by successful bile drainage.