In the current study, we first reported that sepsis per se markedly promoted the expression of Nrp-1 on CD4+CD25+Tregs in a grade- and time-dependent manner, the expression of Nrp-1 on Tregs was obviously correlated with the expression of Foxp-3 and the mortality of CLP-induced septic mice, and Nrp-1 had prevented ability to preserve the negative immunoregulation of Tregs in sepsis. The gene discussed is CD4; the disease is Sepsis.