Objective To investigate the role of dynophin and substance P in pruritus with 5/6 subtotal nephrectomy rats (STNx). Methods 5/6 subtotal nephrectomy rots were prepared. After 24 weeks , STNx rats entered in end stage renal disease(ESRD). Sixty male SD rats were divided into 4 groups, STNx+P group(n=15), STNx+dynophin group( n=15), STNx control group(n=15) and sham operation group(n=15). Substance P (SP), dynophin and saline were intradermal injected separately. After injection, scratch reaction of rats in 30 minutes were recorded. And then SP concentration in blood was estimated by ELISA and SP expression in skin was examined by immunohistochemisty. Results SP concentration in blood of STNx rats were (1010.2±103.5)pg/ml, which increased to (2530.0± 236.3) pg/ml in STNx+SP group and decreased to (612.4±72.2)pg/ml in STNx+dynophin group, and it was the lowest in sham opera- tion group (240.2±36.5)pg/ml. SP expression in skin was similar to that of in blood. The scratch times in STNx+SP group were highest (7.3±1.9 times), there was no significant difference between STNx + dynophin group and STNx control group. Conclusion Pruritus in ESRD rats was correlated to the increase of SP in blood and skin. Intradermal injection of dynophin can decrease SP in blood and skin, but can not induce scratch in STNx rats.