As a model organism, zebrafish have many advantages over other animal models and is suitable for studies on establishment of human disease model and mechanism. In zebrafish, there are two phases of endocrine formation during early development, which are directed by concomitant activity of many signaling pathways. Zebrafish pancreas possess similar cell structure with that of other animals, which can express various endocrine hormones including insulin. The main organs required for metabolic control, such as the pancreas, islet, and insulin sensitive tissue (muscle, liver) are conserved in zebrafish, and the mechanisms of glucose regulation in zebrafish is similar to that seen in mammalian models. These render it an excellent model to study glucose metabolism. Hyperglycemia in zebrafish model can be induced by administration of the diabetogenic drug, streptozotocin (STZ), alternatively immersion of the fish in glucose solution and water, or disturbing of signaling pathways associated with glucose metabolism. Glucose levels in adult zebrafish blood or embryo tissue and phenotype of retinal cell layers or retinal vasculature are the commonly used measurement organs in zebrafish diabetic models.