Aim of study:To observe effect of Semen Litchi Effective Constituents (SLEC) on insulin resistance(IR) in rats with Type 2 Diabetes Mellitus(T2DM),and to explore its mechanism.Material and methods:T2DM modelin rats with IR was induced by high-fat feeding combined with streptozocin,then rats were randomly divided into 4 groups:model group,SLEC high-dose group(1.87 g·Kg-1),SLEC low-dose group(0.47 g·Kg-1g)and rosiglitazone group(3.87mg·Kg-1),blank group was established as control.After medication for 4 weeks,effects of SLEC on glucose or lipid metabolism and insulin IR were investigated,histopathology and ultrastructure change of pancreatic tissue were observed,Stem-loop Real-time fluorescence quantitative RT-PCR was used for evaluation of GRP78 mRNA and CHOP mRNA levels in pancreatic tissue of rats.Result:SLEC of High-dose and Low-dose groups can obviously improved fasting blood glucose and glucose tolerance of T2DM rats,there are remarkable difference between SLEC high-dose group and model group(P< 0.01).ISI increased,HOMA-IR index and blood fat level decreased in High-dose and Low-dose groups of SLEC compared with those of model group(P< 0.05,0.01)Histopathology change of pancreatic tissue were alleviated,damaged organelle,such as Endoplasmic reticulum and mitochondria were repaired in both groups of SLEC.Expression levels of GRP78 mRNA and CHOP mRNA levels in pancreatic tissue of both groups of SLEC were obviously lower than those of model group(P<0.05,0.01).Conclusion:SLEC can improve glycolipid metabolism and IR,increase insulin sensitivity to cure T2DM,its effects may be attributed,at least in part,to inhibit the expression of GRP78 mRNA and CHOP mRNA.