Objective To research the protective mechanism of hedysarum polybotys saccharide（HPS） for kidneys of db /db mice with diabetic nephropathy（DN）. Methods Ten 12-week-old male db /m mice were selected as the blank group. Fifty 12-week-old male db /db mice were randomized into the high-dose

middle-dose and lowdose HPS groups

enalapril group and model group

with 10 in each. Each group was given intragastric administration for 8 weeks. The high-dose

middle-dose and low-dose HPS groups were gavaged with 400 mg /（ kg·d）

200 mg /（kg·d） and 100mg/（kg·d） HPS respectively. The enalapril group was gavaged with 10mg/（kg·d） enalapril. The model group and blank group were gavaged with same volume of normal saline. The expressions of vascular endothelial growth factor（ VEGF） and pigment epithelium-derived factor（ PEDF） were detected with immunohistochemical staining and Western blotting. The expressions of VEGF mRNA and PEDF mRNA were detected with RTPCR. Results Comparing with the blank group

the expression of VEGF mRNA was significantly increased but the expression of PEDF mRNA was significantly decreased in the model group（ P < 0. 01）. Comparing with the model group

the expressions of VEGF and VEGF mRNA were significantly decreased but the expressions of PEDF and PEDF mRNA were significantly increased in all administration groups（ P < 0. 05） except the low-dose HPS group.Conclusion HPD can protect the kidneys of DN mice by regulating the expressions of VEGF

PEDF

VEGF mRNA and PEDF mRNA in renal tissue of db /db mice.