To observe the effects of electroacupuncture on the hypothalamic Toll-like receptor 4 (TLR4)/ inhibitor nuclear factor kappa-B α(IκBα)/nuclear factor-κB (NF-κB) signaling pathway in obese insulin resistance (OIR) rats,so as to explore the mechanism of EA underlying improving of insulin resistance. Rats were randomly divided into normal, model and EA groups, with 8 rats in each group. The rat model of OIR was established by feeding with high-fat diet for 8 weeks. EA(2 Hz,1 mA)was applied to unilateral"Zusanli"(ST36),"Fenglong"(ST40),"Zhongwan"(CV12)and"Guanyuan"(CV4)for 10 min, 3 times a week for 8 weeks. The body mass, fasting blood glucose(FBG) and postprandial blood glucose (PBG) were measured before and after 2、4、6、8 weeks' intervention. An intraperitoneal injection glucose tolerance test and hyperglycemic clamps were applied to test insulin resistance. The expression of TLR4、p-IκBα、NF-κB p65、TNF-α、IL-1β mRNA and protein in hypothalamus was detected by quantitative real-time PCR and Western blot, separately. Compared with the normal group, the body mass and PBG of the model group were significantly increased (P<0.01); glucose infusion rate(GIR) was significantly reduced (P<0.01); in the IPGTT test, the increase in blood glucose was significantly greater after 90 and 120 min of glucose injection(P<0.01); the hypothalamus TLR4, NF-κB p65,p-IκBα, TNF-α, IL-1β mRNA and protein expressions were all significantly increased (P<0.01). After EA intervention, the body weight and PBG were significantly down-regulated after 6 weeks and 2 weeks of intervention (P<0.05, P<0.01); GIR were significantly up-regulated after 8 weeks of intervention (P<0.05); In the IPGTT test, the increase in blood glucose 60 min after glucose injection was significantly down-regulated (P<0.05); hypothalamus TLR4, NF-κB p65,p-IκBα, TNF-α, IL -1β mRNA and protein expression were significantly down-regulated (P<0.01). EA can reduce the body weight of OIR rats and improve IR, which may be related to down-regulating the hypothalamic TLR4/IκBα/NF-κB signaling pathway.