Background/Aims: Total parenteral nutrition causes many complications such as cholestasis. Ursodeoxycholic acid is used for the treatment of several cholestatic problems. Metronidazole was investigated before for preventing some components of total parenteral nutrition-associated hepatic dysfunction. This study was designed to investigate the effects of ursodeoxycholic acid alone and ursodeoxycholic acid + metronidazole combination on total parenteral nutrition-associated cholestasis. Methodology: Eighteen rabbits were divided into three groups as follows: group A received a standard formula of total parenteral nutrition only, group B received total parenteral nutrition + ursodeoxycholic acid (3mg/kg/day), and group C were given total parenteral nutrition + ursodeoxycholic acid + metronidazole (25mg/kg/day) for eight days, respectively. Several parameters of liver function tests were compared among these groups. These were transaminases, alkaline phosphatase, total bilirubin, total cholesterol, triglycerides, and serum bile acids. Liver histology was detected in each group at the end of the experiment. Results: In group A, total parenteral nutrition administration resulted in remarkably higher serum values of transaminases, alkaline phosphatase, total cholesterol, total bilirubin, triglycerides, and free bile acids whereas ursodeoxycholic acid administration showed important improvements in the serum values of these parameters in group B animals. The metronidazole group showed nearer or similar laboratory values with group B, but significant differences appeared in bilirubin values (P<0.05) among these groups. Liver histology presented marked differences between group A and group B. Steatosis formed the main component of liver histology in 4 animals out of 6 in group A. Contrary to this, all of the specimens showed normal liver structure except one in group B. In the third group we did not see better morphology than in group B. Conclusions: These results suggested that oral ursodeoxycholic acid therapy during total parenteral nutrition reduces bilirubin levels and improves the other indicators of cholestasis and helps prevent disturbances of liver histology. When it is combined with metronidazole a significant decrease in bilirubin levels has been gained. With the help of ursodeoxycholic acid we can provide enterohepatic circulation of bile acids and regulate lipid metabolism. Metronidazole can be an antibiotic of choice during total parenteral nutrition when needed
