〔Abstract〕 Objective To investigate the changes of lipid biomarkers and lipid metabolic pathways related to liver injury in BTBR ob/ob mice with type 2 diabetes mellitus by biochemical and metabolomics methods. Methods 16 BTBR wild-type(WT) mice(WT group) and 14 BTBR ob/ob obese mice(ob/ob group) at 7 weeks of age were selected and fed in SPF environment until 20 weeks of age. Liver injury was compared between the two groups: The activities of mitochondrial respiratory enzyme complex in liver tissue were detected by high-resolution respirators,and the lipid metabolomic analysis of liver tissue samples in the two groups of mice was performed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry,mainly detecting endogenous metabolites.Principal component analysis( PCA),orthogonal partial least squares discriminant analysis( OPLS-DA) and other models were used to screen potential biomarkers,and the metabolic pathway analysis of the identified metabolites was performed by Metabo Analyst 5. 0. Results Compared with the WT group,the ob/ob group had significantly increased body weight,fasting blood glucose,serum levels of aspartate aminotransferase( AST),alanine aminotransferase( ALT),low-density lipoprotein( LDL-C) and cholesterol( CHO)( P<0. 01). Liver hematoxylin-eosin staining( HE) staining showed that the mice in ob/ob group had structural disorder of liver lobules,swelling of liver cells,a large number of fat vacuoles in cells,diffuse distribution and loose cytoplasm. Oil red O staining showed that there was a large amount of lipid deposition in the hepatocytes of ob/ob mice. The high resolution spirometer showed that the ob/ob mice had mitochondrial oxidative phosphorylation disorder and the activity of complexⅣ decreased. Lipid metabolomic analysis showed that the lipid metabolic profile of ob/ob mice changed,and the metabolic pathways involved mainly included glycerophospholipid metabolism,glycosylphosphatidylinositol( GPI)anchor biosynthesis,triglyceride metabolism,linoleic acid metabolism,α-linolenic acid metabolism and arachidonic acid metabolism. Conclusion The liver injury of ob/ob group mice may be related to the disorder of lipid metabolism,in which the disorder of glycerophospholipid metabolism is the most critical metabolic pathway.