Objective Establish an animal model of small cerebral vascular disease (CVD) in SHR rats induced by D-galactose at various times. Methods Eighteen SHR rats were randomly divided into three groups according to body weight: D-galactose 150 mg / (kg·d) + 4 week, D-galactose 150 mg / (kg·d) + 8 week, and D-galactose 150 mg / (kg·d) + 12 week groups with six rats in each group. Another 6 WKY rats were used as the blank control group. A noninvasive sphygmomanometer was used to monitor blood pressure of rats every week during modeling. The Morris water maze was used to assess the cognitive function of rats after modeling. Brain, thymus, spleen, and liver indexes were measured by the weighing method . T-SOD, GSH-Px, MDA, NEFL and CALB/ SALB contents in rat serum were determined by ELISA. HE and LFB staining were used to observe cell morphology of the prefrontal cortex, ventricular microhemorrhage, and myelin sheath injury of the corpus callosum. Results Compared with the WKY group, the blood pressure of SHR rats was increased with the increase in D-galactose injection time. Learning and memory abilities were decreased significantly. Brain, thymus, spleen, and liver indexes were decreased. T-SOD and GSH-Px contents in serum were decreased, while MDA and NEFL, and CALB/ SALB levels were increased. The number of cytopathic lesions in the prefrontal cortex was increased, the amount of perivascular space and dorsal microbleeding of the third ventricle were increased, and vacuolization of the myelin sheath of the corpus callosum was increased. The most significant pathophysiological changes were observed in rats treated with 150 mg / ( kg·d) D-galactose for 12 weeks. Conclusions SHR rats injected with 150 mg / (kg·d) D-galactose for 12 weeks are a CSVD animal model similar to the human CSVD disease status.