Abstract: OBJECTIVE To investigate the pharmacological activity of different parts and their combinations of Gegen Qinlian Decoction on ADIPOR/AMPK pathway in insulin resistant rats, and to elucidate the pharmacodynamic material basis of Gegen Qinlian Decoction in the prevention and treatment of insulin resistance. METHODS Gegen Qinlian Decoction was divided into total flavonoids, total saponins, total alkaloids and total polysaccharides. The effects of different parts on body posture, four items of blood lipid, insulin resistance index and insulin sensitivity index of insulin resistance rats were investigated. Active sites were comprehensively analyzed and screened. The effects of single and combined use of different parts on ADIPOR/AMPK signal pathway were investigated by ELISA and Western blotting. RESULTS Total flavonoids and total alkaloids in Gegen Qinlian Decoction could significantly improve the abnormal posture, blood lipids and insulin resistance of insulin resistance rats. Total saponins could significantly reduce the content of TC, LDL-C and INS in insulin-resistant rats, and the effect on other indicators was not statistically significant. Therefore, the three parts were combined and administered to investigate the interaction between the parts. The results showed that when the total flavonoids and total alkaloids were used alone or in combination, could significantly increase the expression of ADIPOR, CaMKK2, AMPKα, and p-AMPK in the liver tissue of insulin resistance rats, and could significantly inhibit the expression of SREBP1. Moreover, the combination effect of total flavonoids and total saponins, total alkaloids and total saponins were enhanced, and the effect on ADIPOR, CaMKK2, AMPKα, p-AMPK were significantly different from those when the three were used alone, which indicated that there was an interaction between total flavonoids and total saponins, total alkaloids and total saponins. CONCLUSION The mechanism of Gegen Qinlian Decoction in the prevention and treatment of insulin resistance rats may be achieved through the synergistic activation of ADIPOR/AMPK signaling pathway by total flavonoids and total saponins, total alkaloids and total saponins.