OBJECTIVE: To evaluate the efficacy of Huanglian root decoction(黄连煎剂, HLD) on kidney injury in rat's model of metabolic syndrome(Met S), and investigate the possible mechanism.METHODS: A fructose-induced Met S rat model and human renal tubular epithelial cell-line model were used to compare the efficacy of HLD with that of berberine and tauroursodeoxycholic acid(TUDCA). Blood pressure, biochemical parameters, histopathological changes and the expression levels of oxidative stress markers were evaluated in the animal model at the end of an 8-week treatment regimen. Oxidative stress markers and molecules of the signal pathway of endoplasmic reticulum(ER) stress were evaluated in the human cell-line model.RESULTS: Levels of fasting insulin, systolic blood pressure and diastolic blood pressure were significantly decreased in rats in the Huanglian group compared to those in the Met S group(P < 0.05).Rats treated with HLD and TUDCA exhibited a significant reduction in blood levels of malondialdehyde compared to those in rats in the Met S group(P < 0.05). Significant increases in glutathione peroxidase in human tubular epithelial cells was found in the Huanglian group compared to that in the Met S group(14.02 vs 18.31, P < 0.05). The m RNA expression of protein kinase RNA-like endoplasmic reticulum kinase and eukaryotic translation initiation factor 2 α decreased significantly in Huanglian groups compared with that in the Met S group.CONCLUSION: HLD has therapeutic efficacy on kidney injury in the Met S rat's model, and is non-inferior to berberine and TUDCA.