Insulin resistance, the impaired ability of insulin to stimulate glucose utilization, is a major characteristic of type 2 diabetes. Insulin sensitivity can be measured using a variety of techniques that are commonly employed in diabetes research and care. Of these, hyperinsulinemic-euglycemic clamp is the gold-standard method to assess insulin sensitivity. The euglycemic clamp is widely used in clinics and laboratories to measure insulin action on glucose utilization in humans and animals for clinical and basic science research. Incorporation of radioactive-labeled glucose during euglycemic clamps makes it possible to measure glucose metabolism in individual organs. In recent years, euglycemic clamps have been actively performed in transgenic animal models of obesity, diabetes, and its complications, and have significantly advanced our understanding on the etiology and pathogenesis of type 2 diabetes. This chapter describes our standardized methods of the euglycemic clamp and associated surgical and biochemical procedures to measure insulin sensitivity in conscious rodents.