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Incidence of hepatotoxicity caused by the broad spectrum antibiotic combination amoxicillin-clavulanic acid (Co-amoxyclav) has been increasingly recognized and the mechanism of this toxicity remains undefined. On the other hand, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant therapy in various liver diseases. Therefore, the present study was designed to elucidate the possible role of oxidative stress in hepatotoxicity induced by Co-amoxyclav and the putative protective role of UDCA in rats. Effects of amoxicillin (Amox; 50 mg/kg, orally, 21 d) or clavulanic acid (Clav; 10 mg/kg, orally, 21 d) and their combined administration on the biochemical liver parameters, reduced glutathione (GSH), lipid peroxidation measured as hepatic malondialdehyde (MDA) levels. In addition, myeloperoxidase (MPO) activity and reactive oxygen species (ROS) production in liver homogenate were also evaluated. On the other hand, the protective effects of pretreatment with UDCA (20 mg/kg, orally, 21 d) on these parameters were also evaluated. Our results show that pretreatment with UDCA reduced the liver parameters that were enhanced by single or combined administration of Amox and/or Clav such as serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and serum bilirubin levels. Moreover, pretreatment with UDCA normalized the GSH level and inhibited the elevation in hepatic MDA concentration. The enhanced MPO activity and ROS production in liver homogenate of rats treated with Clav or Co-amoxyclav were also normalized by UDCA pretreatment. In conclusion, the …