Abstract: Background　Oxidative stress induces the senescence of pancreatic islet β cells, impairs the function of pancreatic islet β cells, and exacerbates the progression of type 2 diabetes. Objective　To investigate the effect of mesenchymal stem cellderived exosomes (MSC-EVs) on oxidative stress-induced senescence of pancreatic islet β -cells and the underlying mechanisms. Methods　A β -cell senescence model was established by treating MIN6 cells with H2O2, followed by intervention with various concentrations of MSC-EVs. Senescence-associated β -galactosidase staining, flow cytometry, quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), and immunofluorescence (IF) were used to detect the expression changes of senescence-related markers. Conditioned media were collected from the senescence group and the MSC-EVs-treated group, which were then applied to normal MIN6 cells. After intervention, the expression levels of mature functional genes insulin(INS) and pancreatic duodenal homeobox1(PDX1) and dedifferentiation marker genes aldehyde dehydrogenase 1 family member A3 (ALDH1A3) and neurogenin3(NGN3) were measured. Results　MSC-EVs treatment decreased the percentage of senescenceassociated β -galactosidase-positive cells (decreased by 2.1 fold compared with the H2O2 induced model group, P＜0.001) and downregulated the expression of cell cycle regulatory proteins P16 and P21 (mRNA levels were reduced by 1.8 fold and 2.1 fold, respectively, relative to the model group, P＜0.01), alleviating the senescence of pancreatic β-cells under oxidative stress. Moreover, following MSC-EVs treatment, the secretion of senescence-associated secretory phenotype (SASP) factors from senescent β -cells was reduced. Consequently, the expression of mature β-cell identity genes INS and PDX1 was preserved, while the upregulation of dedifferentiation marker genes ALDH1A3 and NGN3 was attenuated in the surrounding β -cells. Conclusion　MSC-EVs protect islet β -cell function and improve glycemic control by alleviating oxidative stress-induced β -cell senescence and reducing SASP secretion, thus offering a novel potential therapeutic strategy for type 2 diabetes mellitus.