Glucagon and insulin are the main regulatory factors for blood glucose and jointly maintain the homeostasis of energy me-tabolism in the body,but the internal mechanism of the mutual regulation and influence between them remains complex and unclear.The liver is one of the key target organs for both insulin and glucagon,playing a crucial role in maintaining the homeostasis of glucose and lipid metabolism.Insulin resistance is often accompanied by abnormal glucose and lipid metabolism in the liver,which may affect the functional activity of glucagon in the liver.There is a glucagon-related feedback loop between the liver and the pancreas,known as the"liver-α-cell axis",which may play a critical role in understanding the metabolic effect of glucagon in the state of insulin resis-tance.In addition to the regulation of glucose homeostasis,the physiological action of glucagon has been extended to lipid and amino acid metabolism.Therefore,abnormal regulation of glucagon metabolism may further lead to the imbalance of glucose,lipid,and amino acid metabolism.This article briefly reviews the regulatory mechanism of glucagon in liver glucose homeostasis,lipid metabolism,and amino acid metabolism in physiological condition and the state of insulin resistance.