Long-term total parenteral nutrition (TPN) is known to be associated with cholestasis and hepatic steatosis, which can be lethal in infants who cannot be fed orally. The present review focuses on the metabolic complications in the liver that may occur due to the excessive administration of fat-free TPN. We have recently developed an infant rat model of hepatic dysfunction and steatosis induced by overdose of fat-free TPN. In this model, plasma levels of liver enzymes in the fat-free TPN group were found to be significantly higher than in the other groups (i.e., the oral diet and fat-containing TPN groups). Pathological examination showed hepatomegaly and severe fatty changes without cholestasis in the liver of infant rats that received fat-free TPN. We clearly demonstrated that the addition of soybean oil emulsion to the TPN regimen prevented hepatic dysfunction and fatty changes. In the present review, we discuss the molecular mechanism of the hepatic dysfunction induced by fat-free TPN and the role of soybean oil fat emulsion in the TPN regimen. We also discuss the clinical implications of soybean oil-containing TPN solutions and point out the importance of including fat in the TPN regimen in order to prevent the hepatic abnormalities associated with the excessive administration of fat-free TPN.