Insulin resistance in humans and mice is an important hallmark of metabolic diseases. Therefore, assessment of insulin sensitivity/resistance in animal models provides valuable information in the pathophysiology of diabetes and obesity. Depending on the nature of the information required, we can choose between direct and indirect techniques available for the determination of insulin sensitivity. Thus, the complex hyperinsulinemic-euglycemic glucose clamps and the insulin suppression test assess insulin-mediated glucose utilization under steady-state conditions, whereas less complex methods, such as the insulin tolerance test (ITT), rely on measurements of blood glucose levels in animals subjected to intraperitoneal insulin loading. Finally, surrogated indexes derived from blood glucose and plasma insulin levels are also available for assessment of insulin sensitivity/resistance in vivo. In this chapter, we focus on the intraperitoneal insulin tolerance test (IPITT) protocol for measuring insulin resistance in mice.