Studies focused on the development of diabetes in NOD mice-a model for human type 1 diabetes-have revealed that an autoimmune inflammatory process is produced by the effect of Th1 cells and their secreted cytokines. DNA vaccination has been shown to be an effective method for modulating immunity in viral infections and experimental autoimmune diseases, including diabetes. VIP's immunomodulatory properties are partly mediated by skewing the pattern of cytokines from a proinflammatory response to an anti-inflammatory response. Using gene delivery to express VIP, we interfered in the immune process leading to diabetes in prone, cyclophosphamide-treated NOD mice. Our results extend the role of VIP in the control of immunoregulatory networks and open new perspectives for immunointervention through VIP-based gene therapy.