Objective The purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line(EL-4 cells) was used. The expressions of CD4,CD25,Nrp1,calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1,IL-10,PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation,the expression of Nrp1 increased significantly in 4.0 Gy group,compared with sham-irradiation group(P<0.05) in the spleen and thymus,respectively,when ICR mice received whole-body irradiation(WBI). Meanwhile the synthesis of Interleukin 10(IL-10) and transforming growth factor-β1(TGF-β1) increased significantly after high dose irradiation(HDR)(> or = 1.0 Gy). In addition,the expression of cAMP and PKA protein increased,while PKC-α,calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation,this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice. Objective The purpose of the present study was to observe the changes in CD4 + CD25 + Nrp1 + Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line (EL-4 cells) was used The expressions of CD4, CD25, Nrp1, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1, IL-10, PKA and cAMP were estimated with ELISA. Nrp1 increased significantly in 4.0 Gy group, compared with sham-irradiation group (P <0.05) in the spleen and thymus, respectively, when ICR mice received whole-body irradiation (WBI). Meanwhile the synthesis of Interleukin 10 (IL- and increased transforming growth factor-β1 (TGF-β1) increased significantly after high dose irradiation (> or = 1.0 Gy). In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibi ted when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4 + CD25 + Nrp1 + Treg cells after ionizing radiation. indicated that HDR might induce CD4 + CD25 + Nrp1 + Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.