Insulin dependent diabetes mellitus is a chronic metabolic disease. Many drugs used in its treatment which have a number of serious adverse effects. Natural agent as quercetin (QCT) has been suggested in the alternative medicine for treatment of diabetes mellitus. To evaluate the effect of QCT on the histological changes which occur in the islet of Langerhans of the streptozotocin (STZ)-induced diabetic rats and the possible mechanisms through which QCT produces its protective effect. Fourty five male albino rats were divided into 3 groups: Group I, control group; 15 rats received single intraperitoneal injection of citrate buffer saline. Group II, diabetic group; 15 rats received single intraperitoneal injection of STZ. Group III; QCT-treated group, 15 rats received daily intraperitoneal injections of QCT for 30 days prior to, and for 30 days after the single injection of STZ. Blood samples were taken for monitoring blood glucose levels. Pancreas was taken out and processed for light microscopic, immunocytochemical and morphometrical studies.