Streptozotocin (STZ) is an antibiotic that can cause pancreatic β‐cell destruction, so it is widely used experimentally as an agent capable of inducing insulin‐dependent diabetes mellitus (IDDM), also known as type 1 diabetes mellitus (T1DM). This unit describes protocols for the production of insulin deficiency and hyperglycemia in mice and rats, using STZ. These models for diabetes can be employed for assessing the mechanisms of T1DM, screening potential therapies for the treatment of this condition, and evaluation of therapeutic options. Curr. Protoc. Pharmacol. 40:5.47.1‐5.47.14. © 2008 by John Wiley & Sons, Inc.