Abstract: To explore the effects of extract of selenium-enriched Astragalus membranaceus(ESAM)on insulin resistance(IR)in streptozotocin(STZ)diabetic rats. In this study, type 2 diabetes mellitus(T2DM)was established; ESAM and pioglitazone were used to intervene T2DM model rats; the general condition of rats in each group was observed, and body weight and fasting blood glucose(FBG)were recorded before modeling and after modeling. At the end of the fourth week, the blood and liver tissues of each group were collected. The total cholesterol(CHOL), triglyceride(TG), high-density lipoprotein(HDL), low-density lipoprotein(LDL)in blood were detected by biochemical detector; ELISA was used to detected content changes of blood fasting insulin(FINS), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), C-reactive protein(CRP), interleukin-1β(IL-1β); Western blotting was used for the detection of insulin receptor substrate protein 1(IRS1), phosphorylated IRS1(p-IRS1), nuclear factor κB inhibitor kinase β(IKKβ), phosphorylated IKKβ(p-IKKβ), c -Jun N-terminal kinase(JNK), phosphorylated JNK(p-JNK)protein changes. Results showed that compared with the blank group, the body weight of the model group was significantly decreased. FBG, CHOL, TG, LDL, TNF-α, IL-6, CRP, IL-1β in the blood and p-IRS1, p-IKKβ, p-JNK in the liver was increased significantly; after intervention, pioglitazone, ESAM can reverse the body weight of the model rats and the changes of the above cytokines and proteins. In conclusion, ESAM can reduce the expression of inflammatory cytokines in T2DM rats, inhibit the increase of free fatty acids(FFA), decrease the activation of IKKβ and JNK phosphorylation in surrounding tissues, activate insulin pathway and improve the IR effect of T2DM.