Transgenic liver-specific inactivation of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM1) impairs hepatic insulin clearance and causes hyperinsulinemia, insulin resistance, elevation in hepatic and serum triglyceride levels, and visceral obesity. It also predisposes to nonalchoholic steatohepatitis (NASH) in response to a high-fat diet. To discern whether this phenotype reflects a physiological function of CEACAM1 rather than the effect of the dominant-negative transgene, we investigated whether Ceacam1 (gene encoding CEACAM1 protein) null mice with impaired insulin clearance also develop a NASH-like phenotype on a prolonged high-fat diet. Three-month-old male null and wild-type mice were fed a high-fat diet for 3 months and their NASH phenotype was examined. While high-fat feeding elevated hepatic triglyceride content in both strains of mice, it exacerbated macrosteatosis and caused NASH-characteristic fibrogenic changes and inflammatory responses more intensely in the null mouse. This demonstrates that CEACAM1-dependent insulin clearance pathways are linked with NASH pathogenesis.