Prostate cancer (CaP) is one of the most common types of cancer among men and the second leading cause of cancer-related death in western countries. The risk factors for CaP are age, race/ethnicity, family history and diet. It is interesting that epidemiologic evidence suggests a history of diabetes mellitus (DM) is related to a decreased CaP risk. The cause of this association remains largely unknown. DM is a group of metabolic diseases characterized by hyperglycemia and insulin resistance. It is commonly associated with microvascular complications including diabetic retinopathy, nephropathy and neuropathy. The typical histological changes of microvascular lesions are capillary basement membrane thickening, capillary occlusion and degeneration, eventually capillary dysfunction and organ ischemia. Therefore, we hypothesize that DM might induce local microvascular dysfunction and prostate ischemia, which prevent initiation and development of CaP. Currently, numerous studies showing effect of anti-angiogenesis therapy on CaP strongly support our hypothesis.