Abstract：Objective：To discuss improvement effect of polydatin on insulin resistance(IR) in rats with type 2 diabetes and its mechanism. Methods： A total of 100 SD rates at SPF level were randomly divided into the control group， the model group， the pioglitazone group， and the polydatin groups of low and high dose， 20 rats in each group. Except the control group， the rat models with type 2 diabetes were established through intraperitoneal injection of streptozotocin in other groups. On the 1st day after successful establishment，the pioglitazone group and the polydatin groups of low and high dose were given gastric perfusion with corresponding medicine；the control group and the model group were given normal saline of same volume. After experiment，the relevant indexes of IR were determined；the levels of mRNA and protein of insulin receptor substrate-1(IRS-1) in the pancreas and glucose transporter-4(GLUT-4) were determined by RT-PCR method and Western blot method. Results： Compared with those in the control group， the levels of fasting plasma glucose(FBG)， fasting insulin(FINS) and homeostasis model assessment of insulin resistance(HOMA-IR) in the model group were increased (P＜0.05)；the levels of homeostatic model assessment of islet β cell function(HOMA- β) and quantitative insulin sensitivity check index(QUICKI)，and the levels of mRNA and protein of IRS- 1 in the pancreas and GLUT-4 were decreased(P＜0.05). Compared with those in the model group，the levels of FBG，FINS and HOMA-IR in the pioglitazone group and the polydatin groups of low and high dose were decreased(P＜0.05)；the levels of HOMA- β and QUICKI，and the levels of mRNA and protein of IRS-1 in the pancreas and GLUT-4 were increased(P＜0.05). Compared with those in the pioglitazone group，the levels of FBG， FINS and HOMA- IR in the polydatin groups of low and high dose were increased(P＜0.05)； the levels of HOMA-β and QUICKI，and the levels of mRNA and protein of IRS-1 in the pancreas and GLUT-4 were decreased(P＜0.05). Compared with those in the low-dose polydatin group，the levels of FBG，FINS and HOMA-IR in the high-dose polydatin group were decreased(P＜0.05)；the levels of HOMA- β and QUICKI，and the levels of mRNA and protein of IRS- 1 in the pancreas and GLUT- 4 were increased(P＜0.05). Conclusion： Polydatin can significantly improve IR in rats with type 2 diabetes. Its mechanism probably is that polydatin can promote the expression of mRNA and protein of IRS- 1 in the pancreas and GLUT-4，and then activate IRS-1 signaling pathway.