Objective To investigate the effects of Liuwei Dihuang Tang (LWDHT, Six-Ingredient Rehmannia Decoction) on the expression of proline Hydroxylase2 (PHD2) and hypoxia inducible factor alpha-1 (HIF-1α) in renal tissue of rats with chronic renal failure, and to investigate the pathogenesis and molecular mechanism of LWDHT in preventing and treating chronic kidney disease.Methods 60 SD rats were randomly divided into sham-operation group, model group, LWDHT low-dose, medium-dose and high-dose groups, and chronic renal failure model group (5/6 nephrectomy).The LWDHT low-, medium and high-dose groups were treated with 3.38 g/(kg·D), 6.75 g/(kg·D) and 13.5 g/(kg·D) Liuwei Dihua Decoction respectively.Sham-operation group and model group were given 10 mL/(kg·D) saline once per day for 12 weeks.At 12 weeks, 24 h urinary protein, blood urea nitrogen, and serum creatinine were measured and morphological changes of renal tissues in rats of all groups were observed with H&E staining method;protein level and gene expression of PHD2, HIF-1α in rat renal tissue were evaluated by using immunohistochemical method and RT-PCR.Results 24 h urine protein, blood urea nitrogen and serum creatinine of rats in the model group were significantly higher than those in the sham-operation group (P<0.05).These values in LWDHT low-, medium-, and high-dose groups were significantly lower than those of model group (P<0.05).HE staining results showed that renal interstitial fibrosis was not detected in sham-operation group but significant in model group;renal interstitial fibrosis was significantly reduced in the LWDHT low-, medium-, and high-dose groups.Compared with sham-operation group, levels of PHD2 protein and mRNA expression in renal tissue of model group were significantly lower (P<0.05);levels of HIF-1α protein and mRNA expression were markedly increased (P<0.05).Compared with the model group, levels of PHD2 protein and mRNA expression in rats' kidney tissue in LWDHT low-, medium-, and high-dose groups were significantly increased (P<0.05), and expressions of HIF-1α protein and mRNA were significantly decreased (P<0.05).There was a negative correlation between the expression of PHD2 and HIF-1α mRNA (r=-0.653, P=0.00).Conclusion PHD2/HIF-1α signaling pathway seems to be involved in renal interstitial fibrosis, and Liuwei Dihuang Decoction could effectively prevent and act against chronic kidney disease.Its mechanism may be related to the up-regulation of PHD2, and down-regulation of HIF-1α.