OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX) on renal fibrosis induced by unilateral ureteric obstruction(UUO), and on reactive oxygen species(ROS) homeostasis in human umbilical vein endothelial cells(HUVECs).METHODS:Forty male mice were randomly divided into six groups, sham group, UUO group, UUO+resveratrol(RSV)(15 mg/kg) group, UUO + YSHX20 mg/kg group(UUO + YSHX-L), UUO + YSHX 40 mg/kg group(UUO + YSHX-M), UUO + YSHX 80 mg/kg group(UUO + YSHX-H). Western blotting was used to measure protein expression levels. Reverse transcription-quantitative polymerase chain reaction was used to measure the m RNA expression. Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample. Cell apoptosis was measured by Annexin V/PI staining. Cell viability was measured using CCK-8/WST-8 assay.RESULTS:YSHX treatment reduced α-SMA and Col-4 expressions, and increased CD31 and VE-cadherin expressions in UUO model mice. In vitro, YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions. YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor coactivator-1α(PGC-1α)/silent mating-type information regulation2 homolog 3(Sirt3) signaling.CONCLUSION:YSHX treatment reduced 109 KJ UUO-induced renal injury and fibrosis. Furthermore, YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.