Objective: To investigate long-term effects of oral vitamin C administration on the cerebral microvascular vasodilation in diabetes, using streptozotocin (STZ)-induced diabetic rats. Materials and methods: Diabetes was induced in male Wistar Furth rats by a single intravenous injection of STZ (55 mg/kg b.w). Ascorbic acid (vitamin C) was administered in drinking water (1g/l). The rats were divided into control and diabetic groups with or without administration of vitamin C. The cerebral microcirculation was observed at different times (12, 24 and 36 weeks) after vitamin C supplementation, using fluorescence videomicroscopy. Responses of cerebral arterioles to acetylcholine (ACh), adenosine-5 diphosphate (ADP) and nitroglycerine (NTG) were studied by measuring diameters of cerebral arterioles before and after topical application on the cortical surface. Results: The vasodilatory responses of cerebral arterioles to ACh and ADP were significantly decreased in diabetic rats, compared with non-diabetic (control) rats. The response to NTG was not altered in diabetic rats, indicating that the vasodilatory impairment involves at the endothelium. The impaired endothelium-dependent vasodilation was prevented by long-term vitamin C administration.