We investigated the contributions of dietary fat and dietary carbohydrate to the development of fatty liver induced by western diet (WD). Compared with WD-fed wild type (WT) mice, livers of WD-fed ChREBP(-/-) mice showed lipid droplets of varying sizes around the hepatic lobules, while hepatic triglyceride and cholesterol contents were only modestly decreased. Inflammation and fibrosis were suppressed in ChREBP(-/-) mice. In addition, compared with WD-fed WT mice, ChREBP(-/-) mice showed decreased β-oxidation, ketogenesis and FGF21 production, increased intestinal lipid absorption, and decreased VLDL secretion. These findings suggest that dietary fat and carbohydrate contribute differently to the development of fatty liver.