ObjectiveTo evaluate the formation and mechanism of non-alcoholic fat liver disease (NAFLD) in three species of rodents by analyzing effect of species differences on replication of NAFLD models. MethodsTwenty SD rats, 20 ICR mice and 20 Mongolian gerbils were assigned randomly into 2 groups respectively:model group (fed with high fat diet) and control group (fed with normal diet). After 16 weeks, hepatic pathology was observed with HE and Mallory''s trichrome staining, and serum lipid levels (CHO, TG, LDL-c, HDL-c) and liver function (GOP, GPT), liver index, antioxidant enzyme activity (SOD, GSH-PX, CAT), hydroxyproline, free fatty acid, MDA of liver were detected. ResultsCompared with the control group, Hyp, CHO, TG, LDL-c, HDL-c, liver index, GOP, GPT, MDA, FFA were significantly increased, whereas SOD, GSH-PX, CAT were significantly decreased in Mongolian gerbils (P<0.05, P<0.01); pathology showed hepatic fibrosis; CHO, liver index, GOP, GPT, FFA, SOD were significantly increased, whereas MDA, GSH-PX, CAT were significantly decreased in SD rats (P<0.05, P<0.01), and formed focal non-alcoholic steatohepatitis; CHO, LDL-c, HDL-c, liver index, CAT were significantly increased, whereas MDA was significantly decreased in ICR mice (P<0.05, P<0.01), and the liver histology was normal. ConclusionsThere are obviously statistical differences in lipid metabolism, liver function and oxidative stress among the three species of rodents. They form different NAFLD models:Mongolian gerbils form liver fibrosis model with high TG, CHO, SD; rats form focal fatty hepatitis with high CHO; and ICR mice form hypercholesterolemia model without pathological changes in the liver.