The invention provides a T2D mouse comprising a progeny from mating a C57BL/6 mouse and a DBA/2 mouse and exhibiting a blood glucose level of at least about 200 mg/dl, wherein the mouse is a non-human mammalian model predictive of human type 2 diabetes. The T2D mouse also can exhibit impairment of glucose tolerance, normal or increased insulin production, impaired adipocyte or muscle glucose transport or decreased expression of at least one polypeptide involved in insulin action. Further provided is a method of producing a non-human mammal predictive of type 2 diabetes. The method includes mating a C57BL/6 mouse with a DBA/2 mouse, and backing crossing offspring of the mating with a parental DBA/2 mouse to produce a progeny exhibiting a blood glucose level of at least about 200 mg/dl that is predictive of human type 2 diabetes. A method of screening for a therapeutic agent for use in treating type 2 diabetes also is provided. The method includes: (a) administering a compound to the mouse of claim 1, and (b) screening the mouse for a reduced symptom of type 2 diabetes, thereby identifying a therapeutic agent for use in treating type 2 diabetes.