Abstract： Objective： To explore the efficacy and mechanism of Qidan Formula in improving insulin resistance （IR） in type 2 diabetes mellitus （T2DM） rats. Methods： A total of 60 Wistar rats were randomly divided into six groups：the normal group，the model group，the low-dose Qidan Formula （Qidan-L） group，the high-dose Qidan Formula （Qidan-H） group， the inhibitor group， and the positive control group， with 10 rats in each group. Except for the normal group， T2DM rat models were established in the other groups through high-sugar and high-fat diet combined with intraperitoneal injection of Streptozotocin （STZ）. After successful modeling， the Qidan-L and Qidan-H groups were given Qidan Formula at doses of 5.58 g（/ kg·d） and 11.16 g（/ kg·d） by gavage，respectively. The positive control group was given Metformin at 0.16 g（/ kg·d） by gavage，and the inhibitor group was given Qidan Formula at 11.16 g/（kg·d） by gavage along with intraperitoneal injection of phosphatidylinositol 3-kinase （PI3K） inhibitor solution at 1 mg（/ kg·d）. Fasting blood glucose （FBG） were compared before and after intervention. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C），and fasting insulin （FINS） were compared，and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. The mRNA levels of PI3K，protein kinase B （AKT），forkhead box protein O1 （FoxO1）， and phosphoenolpyruvate carboxykinase （PEPCK） in liver tissues were compared. The protein expressions of PI3K， phosphorylated PI3K （p-PI3K） ， AKT， phosphorylated AKT （p-AKT） ， FoxO1， phosphorylated FoxO1 （p-FoxO1）， and PEPCK in liver tissues were also compared. Results： Before intervention， FBG levels in the drug intervention groups and the model group were higher than those in the normal group （P＜0.05）. After intervention，FBG levels in the model group remained higher than those in the normal group （P＜0.05）；FBG levels in the Qidan-H and positive control groups were lower than those in the model group （P＜0.05）. Compared with the normal group，TC，TG，and LDL-C levels in the model group were increased （P＜0.05），while HDL-C levels were decreased （P＜0.05）. Compared with the model group，TC，TG，and LDL-C levels in the Qidan-L，Qidan-H， inhibitor， and positive control groups were decreased （P＜0.05）， while HDL-C levels were increased （P＜0.05）. Compared with the Qidan-L group， TC， TG， and LDL-C levels in the Qidan-H and positive control groups were decreased （P＜0.05），while HDL-C levels were increased （P＜0.05）. Compared with the inhibitor group，TC，TG， and LDL-C levels in the Qidan-H and positive control groups were decreased （P＜0.05），while HDL-C levels were increased（ P＜0.05）. Compared with the normal group，HOMA-IR levels in the model group were increased（ P＜0.05）. Compared with the model group， HOMA-IR levels in the Qidan-L， Qidan-H， and positive control groups were decreased（ P＜0.05）. Compared with the Qidan-L group，HOMA-IR levels in the Qidan-H and positive control groups were decreased （P＜0.05）. Compared with the inhibitor group，HOMA-IR levels in the Qidan-H and positive control groups were decreased （P＜0.05）. Compared with the normal group，PI3K and AKT mRNA expressions in the model group were downregulated （P＜0.05）， while FoxO1 and PEPCK mRNA expressions were upregulated （P＜0.05）. Compared with the model group，PI3K and AKT mRNA expressions in the Qidan-L，Qidan-H，and positive control groups were upregulated （P＜0.05）， while FoxO1 and PEPCK mRNA expressions were downregulated （P＜0.05）. Compared with the Qidan-L group，PI3K and AKT mRNA expressions in the inhibitor group were downregulated （P＜ 0.05），while FoxO1 and PEPCK mRNA expressions were upregulated （P＜0.05）. Compared with the inhibitor group， PI3K and AKT mRNA expressions in the Qidan-L， Qidan-H， and positive control groups were upregulated （P＜ 0.05），while FoxO1 and PEPCK mRNA expressions were downregulated （P＜0.05）. Compared with the normal group， p-PI3K， p-AKT， and p-FoxO1 protein expressions in the model group were decreased （P＜0.05）， while PEPCK protein expression was increased （P＜0.05）. Compared with the model group， PI3K， p-PI3K， p-AKT， and p- FoxO1 protein expressions in the Qidan-L，Qidan-H，and positive control groups were increased （P＜0.05），while PEPCK protein expression was decreased （P＜0.05）. Compared with the Qidan-L group，PI3K，AKT，and p-FoxO1 protein expressions in the Qidan-H group were increased （P＜0.05）， while PEPCK protein expression was decreased（ P＜0.05）. Compared with the inhibitor group，PI3K，p-PI3K，p-AKT，and p-FoxO1 protein expressions in the Qidan-H group were increased （P＜0.05）， while PEPCK protein expression was decreased （P＜0.05）. Compared with the positive control group， p-PI3K and p-AKT protein expressions in the Qidan-H group were decreased（ P＜0.05）. Conclusion：Qidan Formula not only reduces body mass and FBG in T2DM rats，downregulates TC， TG， and LDL-C levels， and upregulates HDL-C levels， but also effectively reduces HOMA-IR values. Its mechanism maybe related to the activation of the PI3K/AKT/FoxO1 signaling pathway.