The results revealed that overexpression of FoxO3a in DM + IRI group led to a significant reduction in serum levels of BUN, Cr and MDA, and an increase of SOD content, alleviated histopathological damage to renal tubular epithelial cells, and reduced the expression of renal injury markers KIM1 and NAGL, thereby significantly mitigating tissue damage and renal dysfunction in RIRI (Fig. 6B–E). The gene discussed is FOXO3; the disease is diabetes mellitus.