Introduction: Diabetes, one of the most common chronic diseases worldwide, has many complications and current treatments impose a high cost on health system necessitating that newer treatments be investigated. Type 2 diabetes mellitus is the most common form of diabetes, characterized by insulin resistance and dysfunction of pancreatic beta cells. Considering the restrictions of human studies, animal models of diabetes are appropriate tools for researches. Rodents are the first choice for inducing diabetes mellitus due to their short generation time and economic considerations. There are several animal models of type 2 diabetes, of which, those with both beta cell impairment and insulin resistance are preferable. In the high fat diet-streptozotocin model, as a model of type 2 diabetes, high fat diet induces insulin resistance and streptozotocin causes partial beta cell destruction. The high fat diet-streptozotocin model is a cost-effective and appropriate model for studying type 2 diabetes. In conclusion high fat diet-streptozotocin model has metabolic characteristics similar to those of human type 2 diabetes and can be used for investigating the effects of more recent antidiabetic medications available for the condition.