To estimate whether butylphthalide improves white matter damage and blood-brain barrier disruption by chronic cerebral hypoperfusion and explore its possible mechanism. Methods: 72 Wistar rats were randomly split into three groups with 24 in each: sham group, hypoperfusion group, and butylphthalide group. Permanent bilateral common carotid artery occlusion was used to induce hypoperfusion of the forebrain in hypoperfusion and butylphthalide group rats. Intraperitoneal injection of butylphthalide was administered to butylphthalide group rats after surgery. Microvessel density, Kluver-Barrera’s myelin sheath staining, and quantitative measurement of pre-injected Evans Blue were performed 30 days after surgery. Results: Compared to the control and hypoperfusion group rats, the butylphthalide group rats had a higher microvessel density (P<0.05). Hypoperfusion group rats showed a higher leakage of Evans Blue dye compared to control group rats (P<0.01). Butylphthalide group rats showed a greater leakage of Evans Blue dye than control group rats (P<0.05) but a smaller leakage than hypoperfusion group rats (P<0.05). Hypoperfusion group rats had a lower white matter fiber density than control group rats (P<0.01). Butylphthalide group rats showed a lower white matter fiber density than the control group rats (P<0.05) but a higher density than hypoperfusion group rats (P<0.05). Conclusion: Butylphthalide reduced the white matter impairment caused by chronic cerebral hypoperfusion, and its key mechanism may involve the improvement of microcirculation and the reduction of damage to the blood brain barrier.