This schematic highlights major phases and breakthroughs in T1DM immunotherapy, starting from early animal models in the 1970s (BB rat, insulitis observation), through the identification of autoimmunity and early specific or semi-specific tolerogenic approaches (GAD65, specific inhibitors of IFN-gamma and IL-1β, Tregs), and the use of cyclosporin A. The 1990s marked a period of unsuccessful clinical trials, followed by new strategies such as Tregs, nicotinamide, and anti-CD20 monoclonal antibodies. This evidence concerns the gene IL1B and type 1 diabetes mellitus.