The severe side-effects of Cyclosporin A (CsA) limited its long term clinical application in allograft recipients. In the present study, we investigated the potential synergistic effects of cordyceps sinensis (Cs) with CsA in an allograft kidney transplant rat model. Cs alone or a low dose of CsA treatment did not prolong graft survival. However, the combined therapy of a low dose of CsA with Cs significantly prolonged graft survival in rats. The allografts showed significantly improved function in a combined therapy in rats as determined by urine volume and serum creatinine levels. Furthermore, significantly less mononuclear cell infiltration in kidney grafts, lower levels of CD4+ T cells in peripheral blood, and less serum IL-2 and IFN-gama Production was observed in recipients treated with combined therapy, as compared with recipients treated with Cs alone or a low dose of CsA. These data indicate that Cs and CsA have synergistic effects to block allogeneic graft rejection, which may be applied in transplant recipients to decrease the dose of CsA and avoid CsA associated side-effects.