This study aimed to delineate the potentially beneficial effects of choline on the liver histopathology, antioxidative status and innate immunity in blunt snout bream (Megalobrama amblycephala) fed high-fat diet. Fish[weight:(42.20±0.34) g] were fed four experimental diets containing two dietary lipid levels (5% and 15%) and two choline levels (1200 and 2200 mg/kg) in an indoor circulatory system for eight weeks. After the feeding trial, fish were sampled for analysis of plasma and hepatic lipid metabolites, antioxidant enzymes, haemato-immunological parameters and hepatocyte ultrastructural examination. The results showed that high-fat diet significantly increased liver lipid accumulation, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, malondialdehyde (MDA) concentration, activities of total superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX); meanwhile, high-fat diet remarkably reduced blood leucocyte counts, plasma lysozyme activity, total protein and globulin contents and glutathione (GSH). In addition, obvious ultrastructure abnormalities were observed in the hepatocytes of fish fed 15% lipid and 1200 mg/kg choline with apparent alterations involving mitochondrion, endoplasmic reticulum, nucleus and cell membrane. The results indicated that high-fat diet induced significant liver histological alterations, severe oxidative stress and depressed innate immunity of blunt snout bream. However, high dose of choline in high-fat diet significantly decreased liver lipid content, plasma AST and ALT activities, liver MDA concentration, hepatic SOD and CAT activities, and enhanced blood leucocyte counts and globulin protein level; meanwhile, the structures of hepatocyte organelles were normal. In summary, choline could reduce hepatic excess fat deposition, maintain normal structure and function of liver, and enhance anti-oxidative capacity and innate immunity, and hence it could keep the health of the fish.