Objective: To study the regulatory effect of ultra-filtration extract from Angelice Sinensis Radix and Hedysari Radix(UFEASH) on transforming growth factor-β1(TGF-β1) and Smad signaling pathway of kidney tissue of rat with diabetic nephropathy (DN)

and explore its possible mechanism.Method: The rat model with DN was induced by one-time high-dose (60 mg·kg-1) intraperitoneal injection with streptozotocin (STZ). All experimental rats were divided into blank group

model group

irbesartan group and low

median

high-dose UFEASH groups

and then intragastrically administrated once a day. Fasting blood glucose

urea nitrogen (BUN)

serum creatinine (SCr)

24 h urinary protein were detected after 8 weeks. The changes in renal tissue structure were observed under light microscope. TGF-β1 and smad2/3 content of the rats were tested by ELISA. The expression of TGF-β1

Smad2/3 protein and mRNA expressions in renal tissues were detected by immunohistochemistry and Real-time PCR

respectively.Result: Compared with the normal group

the model group showed significant increases in FBG

BUN

SCr and 24 h urinary protein; ELISA showed notable increases in TGF-β1 and Smad2/3 content

remarkable renal pathological structural abnormality and notable increase in TGF-β1 and Smad2/3 protein expressions (P<0.05

P<0.01). Compared with the model group

UFEASH groups significantly reduced the level of FBG

BUN

SCr and 24 h urine protein of rats with DN (P<0.05). The levels of TGF-β1 and Smad2/3 mRNA expressions were also decreased (P<0.05). The abnormal structure of renal tissue was alleviated. The expression of TGF-β1 and Smad2/3 were reduced (P<0.05

P<0.01).Conclusion: UFEASH can improve renal function in rats with DN and delay the chronic pathological progress of DN

which may be related to the inhibition of TGF-β1/Smad signaling pathway.