The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with ZDF-lean rats that have a defect in pancreatic -cell function, but normal leptin signaling. We have characterized the model with respect to diabetes incidence, age of onset, and longitudinal measurements of glucose, insulin, and lipids, and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 mg/dl and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of -cell decompensation. The incidence of diabetes in male and female rats is 92% and 43% respectively with an average age of onset of 6 months in males and 9.5 months in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry and islet insulin content further support a role for -cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus, diabetes in the UCD-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment and prevention of T2DM.