Liver transplantation has been a successful therapy for liver failure. However, a significant number of recipients suffer from graft dysfunction. Considerably, ischemia and reperfusion (I/R) injury is the most important factor leading to organ dysfunction, although the pathogenesis has not been fully described. I/R injury have several established features that are accompanied by and/or linked to bile duct loss or ductopenia, cholestasis, and biliary ductular proliferations in the posttransplant liver biopsy. However, biliary marker levels increase usually only 5-7 days after transplantation. Intermediate filaments are one of the three cytoskeletal proteins that have a major role in liver protection and maintaining both cellular structure and integrity of eukaryotic cells. We reviewed the canine liver transplantation model as I/R injury model to delineate the intermediate filaments of the cytoskeleton that are probably the determinants in changing the phenotype of hepatocytes to cholangiocytes. Remarkably, this interesting feature seems to occur earlier than frank cholestasis. We speculate that I/R liver injury through a phenotypical switch of the hepatocytes may contribute to the poor outcome of the liver graft.