Background: multiple-organ failure is the chief inducer of death in diabetes mellitus and hyperglycaemiainduced oxidative stress is responsible for serious complications including nephropathy. Medicinal plants with antioxidant activity may ameliorate oxidative status and improve the histological and immunohistochemical lesions resulted in chronic hyperglycemia in diabetes. Aim of the work: this study aimed to assess the beneficial effects of aqueous saffron extract (ASE) in streptozotocin (STZ)-induced diabetic mice by investigating the histopathological and immunohistochemical pattern in kidney tissues of different experimental groups. Material and Methods: fasted mice were intraperitoneally (IP) injected by a single dose of a STZ (60 mg/kg body weight). After 24 hours, animals with fasting blood glucose over than 300 mg/dl were considered diabetic. The experimental groups were; control (1), saffron (2), diabetic (3) and diabetic + saffron (4). The treatment was started on the same day of STZ administration with oral gavage of ASE (80 mg/kg body weight) along with drinking water. At the end of the experimental period (45 days), fasting blood glucose was measured by blood strips using an Accu-Chick Performa device (Germany). Furthermore; histopathological and immunohistochemical studies were performed. Results: Results showed that ASE significantly decreased blood glucose level and caspase-3 immunoexpression in treated diabetic mice as compared to untreated diabetic ones. Moreover, ASE improved the histopathological pattern to show a less injury. Conclusion: administration of ASE showed significant ameliorative effects on the biochemical, histopathological and immunohistochemical parameters in kidney tissues of treated diabetic mice.