Objective To characterize the pathology of cerebrovascular disease in Zucker diabetic fatty (ZDF) rats, to explore its pathogenesis, and to provide a theoretical foundation for the use of the ZDF rat as a model of stroke. Methods Eight male ZDF rats aged 8-9 weeks were fed Purina #5008 feed for 12 weeks and another eight male Zucker lean (ZL) rats were fed standard chow. At the end of this period the body mass, blood glucose, and glycosylated hemoglobin (HbA1c) of each group were compared. Cognitive function was evaluated using a Y-maze test. The morphology of the intracranial vessels was compared using magnetic resonance imaging. Following euthanasia, conventional histopathology and transmission electron microscopy were used to characterize the macrovascular and microvascular lesions in the brain, and immunofluorescence was used to identify albumin leakage and the expression of the tight junction protein zona occludens (ZO)-1. Results The body mass, fasting blood glucose, and HbA1c of ZDF rats were significantly higher than in ZL rats at 20 weeks of age ( P <0. 01), and the time spent in the new arm in the Y-maze test was significantly lower ( P <0. 05). In addition, deformation and segmental stenosis was present in the large blood vessels of the brain, and there was cerebral microvascular occlusion, peripheral nerve fiber edema, albumin leakage around the cerebral blood vessels, and the expression of ZO-1 and occludin protein was lower ( P <0. 01) in the ZDF rats. Conclusions Cognitive dysfunction is present in 20-week-old ZDF rats, and both large and microvessels show vascular stenosis and occlusion in the brain, which is associated with peripheral nerve tissue lesions. The pathogenesis may involve the loss of tight junction proteins, leading to the loss of blood-brain barrier function and an increase in vascular permeability, with consequent functional deficits.