Although the human diet is markedly different from the diets of closely related primate species, the influence of diet on phenotypic and genetic differences between humans and other primates is unknown. In this study, we analyzed gene expression in laboratory mice fed diets typical of humans and of chimpanzees. The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain. Importantly, 10% of the genes that differ in their expression between humans and chimpanzee livers differed also between the livers of mice fed the human and chimpanzee diets. Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes. Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.