Free radicals are implicated in causation of cerebral reperfusion injury and chronic cerebral hypoperfusion in rats is associated with functional and histopathological disturbances. Ocimum sanctum (OS), a plant widely used in Ayurveda, has been shown to possess anti-inflammatory, antioxidant and cognition-enhancing properties. In the present study, we investigated the effect of methanolic extract of OS leaves in cerebral reperfusion injury as well as long-term hypoperfusion. Occlusion of bilateral common carotid arteries (BCCA) for 30 min followed by 45 min reperfusion caused increase in lipid peroxidation and up-regulation of superoxide dismutase (SOD) activity accompanied by fall in tissue total sulfhydryl groups (TSH) in rat forebrains. Ascorbic acid levels were unchanged, however. OS pretreatment (200 mg/kg/day for 7 days) prevented this reperfusion-induced rise in lipid peroxidation and SOD activity. OS pretreatment also stabilized the levels of TSH during reperfusion. Long-term cerebral hypoperfusion (a model of cerebrovascular insufficiency and dementia) induced by permanent occlusion of BCCA for 15 days demonstrated altered exploratory behavior in open-field testing and memory deficits as tested by Morris' water maze. Histopathological examination of hypoperfused animals revealed reactive changes, like cellular edema, gliosis and perivascular inflammatory infiltrate. OS treatment (200 mg/kg/day for 15 days) significantly prevented these hypoperfusion-induced functional and structural disturbances. The results suggest that OS may be useful in treatment of cerebral reperfusion injury and cerebrovascular insufficiency states.