In NOD mice, STAT3 inhibition ameliorated hyperglycemia, reduced pancreatic inflammation, preserved insulin-positive islets, and corrected systemic T cell subset imbalance.<h4>Conclusion</h4>Aberrant activation of the IL-21/STAT3 signaling axis may contribute to impaired Treg function and CD4<sup>+</sup> T cell imbalance in pediatric T1D. This evidence concerns the gene IL21 and type 1 diabetes mellitus.