Objective:To establish a chronic renal failure(CRF)rat model and to investigate the effects of prostacyclin(PGI2)derivatives on the expressions of key factors in renal local renin angiotensin system(RAS)of CRF rats,including angiotensin Ⅱ(AngⅡ),angiotensin(1-7)[Ang-(1-7)],angiotensin converting enzyme 2(ACE2),and angiotensin Ⅱ type 1 receptor(AT1R),thereby to explore the potential protective mechanism of prostacyclin derivatives on CRF. Methods:A total of 30 SD male rats were divided into the sham operation group and the operation group at a ratio of 1∶2. Rats in the operation group underwent 5/6 nephrectomy followed by biochemical and pathological examinations 5 weeks after the surgery to determine the success of modeling,and then the operation group was further randomized into the model group and the treatment group at a ratio of 1∶1. Rats in the treatment group were given beraprost sodium(BPS),a PGI2 derivative at a dosage of 0.6 mg/(kg·d) through two intragastric administrations from the fifth week after operation,and those in the model group and the sham operation group received same volume of distilled water. After 4 weeks of treatment,serum creatinine(Scr)and urea nitrogen(BUN)were detected,and 24-hour urine protein excretion(24 hUPE)was measured. The rats were then sacrificed and pathological changes of renal tissues in rats were observed by HE and Masson staining. Expressions of ACE2 and AT1R in renal tissues were detected by real-time quantitative polymerase chain reaction(qRT-PCR),Western blot and immunofluorescence,and enzyme linked immunosorbent assay(ELISA)was employed to measure the expressions of AngⅡ and Ang(1-7)in kidey and ACE2,AngⅡ,Ang(1-7)and AT1 in serum. Results:24hUPE,Scr and BUN levels were higher in the operation group at 5 weeks and 9 weeks than those in the sham group,with statistical significance. Compared to levels at 5 weeks,Scr and BUN were remarkably decreased in the treatment group at 9 weeks,significantly different from those in the model group with mild reduction,but still higher than those of the model group at 9 weeks,whereas urine protein changed in the opposite direction. Renal pathology showed mesangial cell proliferation and matrix hyperplasia in the operation group,accompanied with changes such as renal interstitial inflammatory cell infiltration,interstitial fibrosis and glomerular sclerosis,on the contrary,above changes were improved in the treatment group. AngⅡ and AT1R in the kidney of the operation group were up-regulated than those in the sham operation group,but Ang(1-7)and ACE2 were down-regulated at the same time. Meanwhile,there were statistical differences in changes of the four factors in RAS in the treatment group,yet no such changes in the kidney were found in the serum. Conclusion:Prostacyclin derivatives reduce the 24 hUPE,relieve the chronic renal fibrosis,and possibly delay the progress of chronic kidney disease via a potential mechanism of regulating the expressions of key factors AngⅡ,ACE2,Ang(1-7) and AT1R in renal local RAS system in the CRF rat model.