It has been demonstrated that prolonged graft survival can be achieved through inhibiting the activation of T cells, and addition of soluble CTLA4Ig and OX40Ig proteins to mixed lymphocyte reactions can effectively inhibit T cell proliferation. To explore the potential of this type of treatment in xenotransplantation, we infected streptozotocin-induced diabetic BalB/c mice (H-2d) (200 mg/kg, IV) with 5×108 pfu AdCTLA4Ig-IRES-OX40Ig on day 1 before islets trans-plantation through the tail vein. The results showed that this treatment prolonged the islet xeno-grafts survival significantly. The reaction to exogenous glucose stimulation was normal and the cytokine secretion of the type Th1 cells was inhibited. The AdCTLA4Ig-IRES-OX40Ig-mediated treatment effectively induced the T cells into anergy and the Th1/Th2 cells into deviation. These results strongly supported the therapeutic potential of blockade of costimulation by Ad-CTLA4Ig-IRES-OX40Ig genes transfer in inducing the organ transplantation tolerance. It has been demonstrated that prolonged graft survival can achieve through inhibiting the activation of T cells, and addition of soluble CTLA4Ig and OX40Ig proteins to mixed lymphocyte reactions can effectively inhibit T cell proliferation. To explore the potential of this type of treatment in Xenotransplantation, we infected streptozotocin-induced diabetic BalB / c mice (H-2d) (200 mg / kg, IV) with 5 × 108 pfu AdCTLA4Ig-IRES-OX40Ig on day 1 before islets trans-plantation through the tail vein. The results said that The treatment prolonged the islet xeno-grafts survival significantly. The reaction to exogenous glucose stimulation was normal and the cytokine secretion of the type Th1 cells was inhibited. The AdCTLA4Ig-IRES-OX40Ig-mediated treatment effectively induced the T cells into anergy and the Th1 / Th2 cells into deviation. These results strongly supported the therapeutic potential of blockade of costimulation by Ad-CTLA4Ig-IRES-OX40Ig genes transfer in inducing the organ transp lantation tolerance.