Diabetic kidney disease (DKD), the most pervasive complication in diabetic patients, has become a major health threat to the aging population. Our previous miRNA profiling identified hsa-miR-223-3p as a dysregulated miRNA in the DKD samples, which may serve as a biomarker for DKD diagnosis. However, the specific mechanism of miR-223-3p in the pathogenesis of DKD remains to be elucidated. In this study, we first verified that miR-223-3p level was significantly decreased in the in vitro cell model and in vivo db/db DKD model, accompanied with endothelial cell damage. Importantly, inhibiting the expression of miR-223-3p exacerbated high-glucose induced damages in Human Umbilical Vein Endothelial Cells (HUVECs) and Human Renal Glomerular Endothelial Cells (HRGECs), while miR-223-3p overexpression showed the opposite effect. We further demonstrated that miR-223-3p associated with IL6T mRNA and attenuated the progression of DKD by suppressing the downstream STAT3 activation, indicative of the implication of miR-223-3p/IL6T/STAT3 axis in the pathogenesis of DKD.(c) 2023 Published by Elsevier Inc.