Objective To explore the possible effect target of removing blood stasis and dredging collaterals herbs in treating diabetic nephropathy（ DN） proteinuria. Methods Among 60 Sprague Dawley rats

ten were randomized as the normal group

and the other rats were established as DN models by feeding high glucose and high fat diet and streptozotocin intraperitoneal injection. The model rats were randomized into the model group（ n = 15）

the irbesartan group（ n = 14） and the herb group（ n = 15）. The irbesartan group was given 13. 5 mg /（ kg·d） of irbesartan tablets. The herb group was given 4. 41 g /（ kg · d） of removing blood stasis and dredging collaterals herbs granules. The normal group and the model group were given equivalent drinking water by gavage

once every day

for16 weeks. 24-hour urinary protein was detected before modeling（ 0 week） and the 2nd

4th

8th

12 th and 16 th week after modeling. At the end of the 16 th week

renal tissue was extracted to be examined pathologically by light microscope. Thickness of glomerular basement membrane was measured. The anionic sites were calculated. The expression levels of renal tissue heparan sulfate proteoglycan（ HSPG）

heparanase（ HPA） and podocalyxin（ PCX）

as well as the urine level of PCX were detected. Results In the 2nd

4th

8th

12 th and 16 th week after modeling

24-hour urinary protein in the model group was higher than that in the normal group at the same time

while 24 hours urinary protein in the irbesartan group and the herb group were lower than that in the model group at the same time. And

in the 12 th and 16 th week after modeling

24-hour urinary protein in the herb group was lower than that in the irbesartan group at the same time（ P < 0. 05 or P < 0. 01）. The thickness of basement membrane were reduced

but the number of the anionic sites increased in the irbesartan group and the herb group compared with those in the model group（ P < 0. 05）. The pathological injuries were improved. There was no significant difference in the levels of expression of renal tissue HSPG protein and mRNA between rats in each group（ P > 0. 05）. Compared with the model group

expression levels of HPA protein and mRNA decreased

expression levels of PCX protein and mRNA increased

and the urine level of PCX decreased in the irbesartan group and the herb group（ P < 0. 05）. Conclusion Removing blood stasis and dredging collaterals herbs might improve proteinuria in DN. The possible mechanism is inhibiting the over expression of HPA in renal tissue. Thus the loss of the anionic sites of basement membrane decreased. The expression of PCX in renal tissue is up-regulated. The excretion of PCX in urine decreased. The integrity of glomerular charge barrier might be maintained.