Abstract: ob＜x＞jective To investigate the effect of empagliflozin on oxidative stress in type 2 diabetic kidney disease(DKD) and its possible mechanism. Methods db/db mice were used as diabetic kidney disease model and randomly divided i nto model group (DM group) and empagliflozin group (DM + EM group), while db/m mice were used as normal control group (NC group). Body weight and fasting blood glucose were recorded. After 8 weeks of continuous administration, blood and urine were collected to measure creatinine (Cr), urea nitrogen (BUN) and urinary microalbumin ( mALB), and renal tissue homogenate was used to detect renal oxidative stress parameters. Masson staining was used to observe the changes of renal fibrosis. qRT-PCR was used to detected the mRNA levels of NF-E2 related factor (Nrf2), quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) . Western blotting was used to detect the protein ex＜x＞pression of Nrf2, NQO1 and HO-1. Results Compared with NC group, Cr, BUN and mALB in DM group were significantly increased, SOD activity and GSH content were significantly decreased, MDA content was significantly increased, the deposition of collagen fibers in renal tissue increased, nuclear Nrf2, NQO1 and HO-1 ex＜x＞pression were significantly decreased; Compared with DM group, Cr, and mALB contents in DM+EM group were significantly decreased, SOD activity and GSH content were significantly increased, renal fibrosis degree reduced, and total Nrf2, nuclear Nrf2, NQO1 and HO-1 ex＜x＞pression were significantly increased. Conclusion Empagliflozin can reduce the level of oxidative stress in renal tissue of diabetic mice by activation of Nrf2 pathway and up regulation of NQO1 and HO-1 protein ex＜x＞pression.