Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can synthesize, glycosylate and assemble mammalian proteins to provide huge quantities of relatively low cost soluble proteins. Furthermore, edible transgenic plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Therefore, the aim of this study was to determine whether a transgenic plant expression system was capable of synthesizing the diabetes-associated autoantigen, glutamic acid decarboxylase (GAD) in an immunogenic form and whether the oral administration of an autoantigen expressed by a plant could directly induce protective immune responses in a mouse model of diabetes. We show that a GAD-expressing transgenic plant, given as a dietary supplement, inhibits the development of diabetes in the non-obese diabetic (NOD) mouse.