Abstract：Objective：To explore the renoprotective effects and metabolic mechanisms of Wuling San in diabetic kidney disease （DKD） mice. Methods：Twenty-four 6-week-old male C57BL/6J mice were randomly divided into a normal group （6 mice） and a modeling group （18 mice）. The modeling group received intraperitoneal injections of 55 mg/kg streptozotocin （STZ） for 5 consecutive days to establish the diabetes model. After successful modeling，the mice were randomly divided into a model group，a Wuling San group，and a perindopril group，with 6 mice in each group. The Wuling San group was given 9.75 g/kg of Wuling San suspension by gavage，the perindopril group was given 0.52 mg/kg of perindopril suspension by gavage， and the normal group and model group were given equal volumes of normal saline by gavage. All groups were administered continuously for 12 weeks. Body weight， 8-hour fasting blood glucose， 24-hour urine volume， and water intake were observed in each group. Twenty-four-hour urinary microalbumin levels were measured. Renal histopathology was observed using periodic acid-Schiff （PAS） staining and hematoxylin-eosin （HE） staining. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry （UPLC-QQQ-MS/MS） was used to detect the levels of branched-chain amino acids （BCAAs） and their metabolites in renal tissues. Results： Compared with the normal group， the model group showed decreased body weight at 4，8，and 12 weeks of intervention，increased 8-hour fasting blood glucose and 24-hour urine volume，and elevated 24-hour urinary microalbumin levels after 12 weeks of intervention （P＜0.05）. Compared with the model group，the Wuling San group and perindopril group showed increased body weight at 8 and 12 weeks of intervention； the Wuling San group showed decreased fasting blood glucose at 4 weeks and decreased 24-hour urine volume at 12 weeks，while the perindopril group showed decreased 24-hour urine volume at 4 weeks；both the Wuling San group and perindopril group showed decreased 24-hour urinary microalbumin levels （P＜0.05）. The model group exhibited widened glomerular mesangial areas， renal tubular vacuolar degeneration， brush border shedding， renal tubular epithelial cell swelling， and focal inflammatory cell infiltration. These pathological changes were alleviated to varying degrees in the Wuling San group and perindopril group. Compared with the normal group， the model group showed elevated levels of leucine，valine，isoleucine，butyryl-L-carnitine，and isobutyryl-L-carnitine in renal tissues （P＜ 0.05）. Compared with the model group，the Wuling San group showed decreased levels of leucine，valine，isoleucine， butyryl-L-carnitine， isobutyryl-L-carnitine， and succinyl-CoA （P＜0.05）. Conclusion： Wuling San exerts renoprotective effects in STZ-induced DKD mice， and its mechanism may be related to the regulation of branchedchain amino acid metabolism disorders in the kidneys.