In the T2DM rat model established by a high-fat diet and streptozotocin (STZ), human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) significantly ameliorated hyperglycemia in T2DM rats, restored insulin receptor substrate1 and the phosphorylation of protein kinase B (tyrosine site), and promoted the expression and membrane translocation of GLUT4 in skeletal muscle. Here, AKT1 is linked to type 2 diabetes mellitus.