Streptozotocin (STZ) is an antibiotic that selectively destroys pancreatic β-cells and is widely used to induce type 1 diabetes mellitus (T1DM) in mice and rats. This article outlines protocols for producing STZ-induced diabetes in mice and rats, as well as models for type 2 diabetes (T2D). These models are used to study the pathological effects of diabetes and to screen potential treatments. STZ is most commonly used in rats and mice, with protocols for inducing T1DM using multiple low-dose STZ injections or a single high-dose injection. For T2D models, nicotinamide is used to partially protect β-cells against STZ, resulting in insulin-deficient but not insulin-resistant T2D. Another model involves high-fat diets to induce insulin resistance, followed by STZ to reduce β-cell function. These models are valuable for studying diabetes and its complications, though they do not perfectly mimic human conditions. The article also discusses critical parameters, animal sensitivity, and troubleshooting for successful model development.Streptozotocin (STZ) is an antibiotic that selectively destroys pancreatic β-cells and is widely used to induce type 1 diabetes mellitus (T1DM) in mice and rats. This article outlines protocols for producing STZ-induced diabetes in mice and rats, as well as models for type 2 diabetes (T2D). These models are used to study the pathological effects of diabetes and to screen potential treatments. STZ is most commonly used in rats and mice, with protocols for inducing T1DM using multiple low-dose STZ injections or a single high-dose injection. For T2D models, nicotinamide is used to partially protect β-cells against STZ, resulting in insulin-deficient but not insulin-resistant T2D. Another model involves high-fat diets to induce insulin resistance, followed by STZ to reduce β-cell function. These models are valuable for studying diabetes and its complications, though they do not perfectly mimic human conditions. The article also discusses critical parameters, animal sensitivity, and troubleshooting for successful model development.