Abstract: This study investigates the metabolic regulatory effects of exogenous lactate on obesity mice induced by high-fat diet.We established obesity and metabolic disorder C57 mice model using a synthetic high-fat forage containing 60% fat.Some mice were fed with high-fat diet for 4 weeks to establish the model, being given 500 mg/(kg?d) lactate with ip for 4 weeks at the same time; the others were fed with high-fat diet for 8 weeks to establish the model, being given 500 mg/(kg?d) lactate 4 weeks after 4 weeks of modeling.During the trial period, the change of body weight and food intake, as well as serum glucose, lactate, triglycerides, insulin, and liver glycogen levels of both groups of mice were measured.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were used to assess glucose metabolism and insulin resistance in the body.At the end of the experiment, adipose tissue was dissected for weighing and histopathological examination.The expression of lipid synthesis and lipolysis genes in adipose tissue was detected by real-time PCR.The results showed that: (1) in the 4-week preventive medication trial, lactate had no significant effect on the body weight of normal and high-fat diet (HFD) mice, yet it increased the subcutaneous fat/visceral fat weight ratio; lactate could significantly reduce fasting blood glucose and liver glycogen levels in HFD mice while increasing blood lactate levels, significantly improving impaired glucose tolerance in HFD mice; lactate could improve the size and arrangement of adipocytes in the HFD group while significantly down-regulating the expression of fatty acid synthesis and lipolysis genes in adipose tissue; (2) in the 8-week treatment, both routes of lactate administration could partially reduce body weight in HFD group mice and reduce food intake, with the improvement trend for fat weight; both routes of lactate administration could significantly reduce fasting blood glucose levels in HFD mice, while significantly improving glucose and insulin tolerance, with some improvement of fasting insulin levels and insulin resistance index; both routes of lactate administration showed different degrees of improvement effect on adipocyte morphology in obese mice while significantly down-regulating lipolysis gene expression in adipose tissue.Therefore, for high-fat diet-induced obese mice with metabolic imbalance, exogenous lactate can stimulate glucose metabolism, inhibit adipose tissue lipolysis, and prevent adipocyte hypertrophy, thereby improving glucose tolerance and insulin sensitivity and reducing sugar-lipid metabolic disorder.