To observe the effects of Shenxikang Granules on kidney pathology，renal function，inflammatory mediators，and the hypoxia-inducible factor-α/hexokinase 2(HIF-α/HK-2) signaling pathway in unilateral ureteral obstruction(UUO) rats，and to explore the mechanism of Shenxikang Granules in improving renal tissue metabolic reprogramming and regulating renal fibrosis.Methods:Eighteen male Sprague-Dawley(SD) rats，SPF grade，with an average body weight of(210±10) g，were used to establish the UUO model.The rats were randomly divided into the following groups：model group，positive control group，and Shenxikang Granules group，according to a random number table，with 6 rats in each group.A sham operation group consisting of 6 SD rats was also set up.Rats in the model and sham operation groups were given deionized water at a dose of 10 mL/(kg·d) by gavage.The positive control group was treated with 1.0 mg/(kg·d) benazepril hydrochloride by gavage，while the Shenxikang Granules group was given 18.2 g/(kg·d) Shenxikang Granules by gavage for 4 weeks.Masson's staining was used to observe kidney tissue pathology.Urine creatinine(UCR) and total urinary protein(UTP) levels were measured.Enzyme-linked immunosorbent assay(ELISA) was used to detect serum creatinine(Scr)，blood urea nitrogen(BUN)，α1-microglobulin(α1-MG)，microalbumin(mALB)，interleukin-18(IL-18)，tumor necrosis factor-α(TNF-α)，and interleukin-1β(IL-1β) expression.The expression of pyruvate(Pyr)，lactate(LA)，adenosine triphosphate(ATP)，HIF-1α，HK-2，transforming growth factor-β(TGF-β)，and α-smooth muscle actin(α-SMA) in kidney tissue was also detected.Results:No abnormalities were found in the kidney tissue of the sham operation group.In the model group，there was a significant increase in blue collagen fibers in the kidney tissue，while the Shenxikang Granules group showed less collagen deposition compared to the model group.Compared with the sham operation group，the model group showed significantly higher levels of UCR，UTP，mALB，Scr，BUN，uric acid(UA)，α1-MG，retinol-binding protein-4(RBP4)，IL-18，TNF-α，IL-1β，monocyte chemoattractant protein-1(MCP-1)，and the expression of Pyr，LA，ATP，HIF-1α，HK-2，TGF-β，and α-SMA in kidney tissue(P<0.01).Compared with the model group，the Shenxikang Granules group showed significantly decreased levels of mALB，BUN，UA，α1-MG，RBP4，TNF-α，IL-1β，Pyr，LA，ATP，HIF-1α，HK-2，TGF-β，and α-SMA(P<0.01，P<0.05).Conclusion:Shenxikang Granules can improve UUO-induced renal fibrosis and restore kidney function.The mechanism of action may be related to the improvement of renal tissue metabolic reprogramming.