We investigated the effects of methimazole, an anti-thyroid drug, on the onset of type 2 diabetes in Zucker diabetic fatty (ZDF) rats. For this, 0.03% methimazole was administered to 7-week-old, pre-diabetic ZDF rats in drinking water for 5 weeks and the animals were sacrificed at 12 weeks of age. Methimazole treatment to ZDF rats significantly reduced blood glucose levels, food intake, body weight, and serum T3 levels. Hepatocytes in ZDF-methi rats were more densely stained with eosin than those in ZDF rats because of low fat accumulation in ZDF-methi hepatocytes. The pancreatic islet in ZDF-methi rats was normal compared to that in ZDF rats. Glucagon, not insulin, immunoreactivity in ZDF-methi rats was significantly higher than that in ZDF-methi rats. These suggest that methimazole treatment may delay the onset of type 2 diabetes in leptin receptor-deficient rats and also suggests that thyroid hormones may be necessary for the onset of diabetes.