The discovery of new treatments for non-alcoholic steatohepatitis (NASH) is made difficult by the lack of a suitable animal model that accurately reflects the biochemical and histological features of the human disease. In this study, we fed Psammomys obesus (an established model of the Metabolic Syndrome) a standard rodent diet (10% of energy derived from fat) supplemented with 2% cholesterol for four weeks. At necropsy, the livers from animals fed the 2% cholesterol diet were grossly enlarged, pale and firm. Liver weight was 2-fold greater in animals on the diet supplemented with cholesterol compared with animals on the standard rodent diet (13.3±0.8 vs 6.8±0.4 g, p<0.001). Correspondingly, liver lipid levels were markedly elevated (283±16 vs 78±8 mg/g, p<0.001). Blinded histopathological analysis confirmed the presence of steatosis, inflammation, cellular injury and fibrosis in the cholesterol supplemented group. Steatosis was marked, with abundant large and small lipid droplets. Inflammation was demonstrated by the presence of neutrophil-containing parenchymal inflammatory foci, and in addition sinusoidal foamy macrophages were seen in some livers. This was supported by greater mRNA expression of CD68 (p=0.001), a marker of macrophage activation. Cellular injury was noted, including focal necrosis in some cases, and there was architectural disruption including fibrous expansion of portal tracts, early septum formation, and both pericellular and perisinusoidal fibrosis. This fibrosis was reflected by markedly higher collagen 1a gene expression (>100-fold, p=0.001). Additionally, the presence of cellular injury in animals fed the 2% cholesterol diet was supported by higher plasma aspartate aminotransferase (AST) levels (144±17 vs 383±88 U/l, p=0.02) and alanine aminotransferase (ALT) levels (92±10 vs 451±127 U/l, p=0.03). These data suggest that P. obesus may be a suitable new animal model of NASH that exhibits the key biochemical, molecular and histological features of the disease in human patients.