To study the effects of nucleoside antiviral drug zidovudine (AZT) on the flexibility of global metabolism and liver glucolipid metabolic balance in mice, male ICR mice were given zidovudine intragastric administration for 12 weeks, and their water and food intake was recorded daily.Serum glucose (GLU) and triglyceride (TG) levels and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected after 12 weeks of administration.Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed.HE staining was used to observe the pathological changes of liver.The gene levels of glucose transporter (Glut2), carnitine palmitate transferase (Cpt1α), medium chain acyl-coa dehydrogenase (Mcad), phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pase) were detected by RT-PCR.Western blot was used to detect the protein levels of insulin signaling Akt, P-Akt, Glut2, Mcad and Cpt1α in liver.The results showed that zidovudine significantly decreased lipid metabolism, impaired glucose tolerance, increased liver cell volume, significantly increased liver triglyceride (TG) and non-esterified fatty acid (NEFA) content, increased Glut2 gene expression, down-regulated fatty acid oxidative metabolism genes Cpt1α, Mcad and gluconeogenesis related genes after fasting, and down-regulated protein expression of Cpt1α.The results suggest that zidovudine can induce the disorder of glucose and lipid metabolism after fasting in a dose-dependent manner.