The induction of immunological self-tolerance begins in the thymus during fetal life. The random recombination of gene segments coding for TCR is followed by the negative selection of T cells bearing a TCR directed against self-antigens presented by thymic MHC. Insulin-like growth factor type 2 (IGF-2) is the dominant gene of the insulin family that is transcribed and translated in the thymus of different species. Contrary to the other members of the insulin gene family, IGF-2 gene (IGF2) is not transcribed in the thymus of diabetes-prone BB rats. The absence of thymic IGF2 expression is associated with the diabetogenic autoimmune process in BB rats. This defect could not only contribute to the lymphopenia of BB rats, but also to the absence of central self-tolerance of the insulin family in this animal.