An animal model of Graves' disease (GD) will help us to clearly understand the role of thyroid-stimulating hormone receptor (TSHR)-specific T cells and TSHR-Abs during the development of GD and to develop TSHR-specific immunotherapy. This review focuses on four different recent approaches towards the development of an animal model of GD. These approaches are: (1) Immunization of AKR/N mice with fibroblasts coexpressing syngeneic major histocompatibility complex (MHC) class II and TSHR. (2) Immunization of selected strains of mice with an expression vector containing TSHR cDNA. (3) Immunization of BALB/c mice with syngeneic M12 cells or xenogenic HEK-293 cells expressing full-length or extracellular domain of TSHR (ETSHR). (4) Injection of adenovirus-expressing TSHR into BALB/c mice.