SRP319724 PRJNA729207 QRXZF modulates gut microbiota and prevents DKD. Given the lack of effective approved drugs to treat diabetic kidney disease (DKD), the traditional Chinese medicine (TCM) characterized with a systematic and integral regulation has become an important treatment for DKD. QRXZF has being used in clinical research. However, the mechanisms of action remain to be defined. In the present study, we identified the renoprotection of QRXZF is probably associated with the modulation of gut microbiota and inhibition of inflammatory response in kidney. The key findings in this manuscript are as follows:Firstly, we demonstrate that QRXZF decreased urinary albumin, regulated lipid metabolism disorder, and reduced the renal histologic injuries in DKD mice with high-fat diet (HFD) and streptozotocin injection-induced.Secondly, we demonstrate that the mechanism of the renoprotection of QRXZF is probably associated with the modulation of gut microbiota, improving the gut barrier and inhibition of inflammatory response in kidney. We also demonstrate that the metabolic inflammation from gut microbiota is a potential mechanism in the heightened risks of inflammatory response and progression of DKD.our study provides evidence for the therapeutic potential of QRXZF in treating DKD.