To explore the mechanism of Yiqi Yangyin Huoxue Formula on improving islet secretion function in rats with type 2 diabetes mellitus(T2DM).Methods:A total of 66 SPF male SD rats were selected,and were randomly divided into a control group with 11 rats and a model building group with 55 rats.The model was fed with high-sugar and high-fat feed combined with streptozotocin to establish a T2DM model.The control group was fed with standard pellet feed and an equal volume of 0.1 mmol/L citric acid-sodium citrate buffer.The successfully modeled rats were divided into a model group,a low,medium and high concentration group of Yiqi Yangyin Huoxue Formula,and the Western medicine group,each with 11 rats.The model group and the control group were given distilled water,the low,medium and high concentration groups of Yiqi Yangyin Huoxue Formula of 0.43 g/mL,0.86 g/mL,1.72 g/mL; the Western medicine group was given 20 mg/mL metformin suspension; the intragastric dose of each group was 10 mL/kg,once a day,for 12 consecutive weeks.Fasting blood glucose(FBG),fasting insulin(FINS),insulin secretion index(HOMA-β),islet cell apoptosis index,islet microribonucleic acid-375(miR-375) and B lymphoma-2(Bcl-2) The expression level of Caspase-3 containing cysteine were tested and compared.Results:Compared with the model control group,the levels of FBG,apoptotic index of islet cells,miR-375 and Caspase-3 expression levels in islet tissues were lower,the levels of FINS and HOMA-β,and Bcl-2 expression levels in islet tissues were higher in each group,the differences were all statistically significant(P<0.05),and Yiqi Yangyin Huoxue Formula group showed a certain dose effect relationship.Conclusion:Yiqi Yangyin Huoxue Formula can reduce blood sugar level in rats with type 2 diabetes mellitus in a dose-dependent manner,improve islet secretion function and inhibit islet cell apoptosis,the effect may be related to inhibiting the expression of miR-375 in islet tissue,and then regulating the expression of apoptosis-related proteins Bcl-2 and Caspase-3.