Abstract： Objective To study the efficacy and mechanisms of blockade of ICOS/B7RP-1 pathway to induce immune tolerance in treatment of rat chronic allograft nephropathy.Methods Orthotopic kidney transplantation was performed following the procedure of Kamada with our modification.All of experimental rats were divided into three groups:group A,isograft group;B,control group(CAN group);C,anti-ICOS antibody group(intraperitoneal injection of anti-ICOS antibody,2 mg/kg twice weekly).The pathological changes were observed at the 4th,8th and 12th week post-transplantation by HE,PAS and Massoa When the transplanted rat survival time exceeded 6 months,CD25 + /CD4+ T cells in peripheral blood were tested by using fluorescence activated cell sorter analysis(FACS).The immunohistochemistry and real-time quantitative PCR were used to detect localization and expression of ICOS in transplant kidney and spleen of the recipients.Results The pathological changes of CAN in control group were significant,and the score according to Banff Standards in control group was higher than in other groups.Anti-ICOS treatment led to a significant decrease of chronic rejection lesions.The population of CD25+ /CD4+ T cells in peripheral blood in group C(13.5 %)was higher than that in group A(9.1 %)(P＜0.05).The expression of ICOS in transplant kidney and spleen of the recipients in group C was down-regulated as compared with group B(P＜0.01).Conclusion Blockade of ICOS-B7RP-1 with anti-ICOS-antibody to induce immune tolerance may attenuate remarkably the development of CAN,and the mechanisms may be the redistribution of ICOS in the spleen of recipients and a high population of CD25+ /CD4+ T cells in peripheral blood.