ObjectiveTo observe the influence of Bupi Yishen decoction on the curative effect of diabetic kidney disease rats and the tubuloglomerular feedback. MethodAmong the 100 SD male rats， 25 were randomly selected as the normal group， and the remaining 75 were treated with high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin （STZ） to establish diabetic rat model. The model rats were randomly divided into model group， Bupi Yishen group and losartan group. Bupi Yishen group and Losartan group were given Bupi Yishen decoction （23.4 g·kg^-1） and losartan tablet （9 mg·kg^-1）， respectively by gavage， and normal group and model group received equal volume of distilled water via intragastric administration. The treatment lasted for 11 consecutive weeks. Random blood glucose was measured once every two weeks. Rats in each group were put into metabolic cage and 24-hour urine volume was recorded. At the end of week 11， the rats were sacrificed for index detection. Enzyme linked immunosorbent assay （ELISA） was used to determine the quantification of 24-hour urinary microalbumin excretion rate （24 h UAER）， renal tubular injury-related proteins and urine creatinine. Blood was collected for creatinine and urea nitrogen detection. Hematoxylin-eosin （HE） staining， periodic acid-schiff （PAS） staining and Masson staining were performed to observe the pathological changes of the kidney of rats. The expression of sodium-glucose cotransporter 1 （SGLT1）， sodium-glucose cotransporter 2 （SGLT2）， sodium-potassium-chloride cotransporter 2 （NKCC2） and connexin 40 （CX40） was detected by immunohistochemistry. The location of adenosine type Ⅰ receptor （A1AR） in kidney was observed by immunofluorescence. In addition， the expression of SGLT1， SGLT2， NKCC2， CX40 and A1AR in renal tissues was determined by Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. ResultCompared with normal group， renal pathology in model group showed increased glomerular volume， thickened basement membrane， and shed renal tubule epithelial cells. Compared with the model group， the renal pathology of bupiyishen group was improved. Compared with normal group， random blood glucose at different time points， 24 h UAER and renal tubule-injury-related proteins were increased in model group （P<0.01）， and the expressions of SGLT1 and SGLT2 in renal tissue were increased （P<0.01）， and the expression of NKCC2， CX40 and A1AR decreased （P<0.01）. Compared with the model group， the random blood glucose， 24 h UAER and renal tubular injury-related proteins in Bupi Yishen group decreased （P<0.01）， the expressions of SGLT1 and SGLT2 were down-regulated， and the expressions of NKCC2， CX40 and A1AR were increased （P<0.05）. ConclusionBupi Yishen decoction can improve glomerular and renal tubular injury and alleviate early hyperfiltration in diabetic kidney disease rats. The intervention effect of Bupi Yishen decoction on diabetic kidney disease is related to the regulation of tubuloglomerular feedback.