Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. Although a significant number of new drugs for NASH are already in the development pipeline, there are no animal models of human (h-) NASH to estimate the efficacy and safety of potential new drugs. We have been producing humanized chimeric mice (PXB-mice) with livers highly repopulated with human hepatocytes (h-heps). These mouse (m-) models are used to study drug metabolism, pharmacokinetics, toxicity of new drugs, and efficacy of anti-hepatitis B and anti-hepatitis C therapeutic agents. In the present study, to develop the h-NASH model, we tried a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) (A06071302; Research Diets, Inc.) in PXB-mice.