Obesity is associated with a state of low-grade chronic inflammation that leads to impairment of insulin signaling pathway. Wheat alkylresorcinols (ARs) are biomarkers and active ingrendients of whole wheat food. In this study, inflammatory factors were used to establish the insulin resistant model in 3T3-L1 adipocytes in vitro, and the protective effect of wheat ARs on insulin resistance of adipocytes in inflammatory state was investigated by measuring the level of lipolysis and glucose uptake of adipocytes. The results showed that wheat ARs had no toxic effect on adipocytes at the concentration of 5~20μmol/L and could improve insulin resistance in 3T3-L1 adipocytes induced by inflammatory factors in a dose-dependent manner, and the glucose uptake increased by 4.3%, 10.2% and 24.0%, respectively. Meanwhile, wheat ARs could significantly alleviate the lipolysis of adipocytes induced by inflammatory factors. In addition, the phosphorylation of Akt (p-Akt) and the expression of its downstream GLUT4 protein in adipocyte glycometa-bolism were significantly reduced by inflammatory factors, leading to glucose uptake disorder. ARs treatment significantly increased Akt phosphorylation and GLUT4 protein expression. After pre-treated with PI3K inhibitor (LY294002), the protective effect of ARs was reversed on 3T3-L1 adipocytes. The phosphorylation of Akt and the expression of its downstream protein GLUT4 were significantly inhibited. Additionally, the lipid accumulation and glucose uptake of adipocytes was inhibited by LY294002, which indicated that ARs could improve insulin resistance and lipolysis of adipocytes via activating p-Akt/GLUT4 signaling pathway. Furthermore, the protective effects of five major homologues of wheat ARs on insulin resistance of adipocytes were compared. These results indicated that heptadecylresorcinol (AR-C17) was the main active substance of wheat ARs.