The prevention of BBB breakdown and the subsequent vasogenic edema are important parts of the medical management of ischemic stroke. The purpose of this study was to investigate the ischemic tolerance effect of Rosmarinus officinalis leaf hydro-alcoholic extract (RHE). Five groups of animals were designed: sham (underwent surgery without MCAO) and MCAO groups, the MCAO groups were pretreated orally by gavages with RHE (50, 75, and 100 mg/kg/day), daily for 30 days. Two hours after the last dose, serum lipid levels were determined and then the rats were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Subsequently, brain infarct size, brain edema and Evans Blue dye extravasations were measured and neurological deficits were scored. Dietary RHE could significantly reduce cortical and sub-cortical infarct volumes (211.55 ± 24.88 mm3 vs. 40.59 ± 10.04 mm3 vs. 29.96 ± 12.19 mm3vs. 6.58 ± 3.2 mm3), neurologic deﬁcit scores, cerebral edema (82.34 ± 0.42% vs. 79.92 ± 0.49% vs. 79.45 ± 0.26% vs. 79.30 ± 0.19%), blood–brain barrier (BBB) permeability (7.73 ± 0.4 μg/g tissue vs. 4.1 ± 0.23 μg/g tissue vs. 3.58 ± 0.3 μg/g tissue vs. 3.38 ± 0.25 μg/g tissue) in doses of 50, 75 and 100 mg/kg/day as compared with the control group in the transient model of focal cerebral ischemia. Although pretreatment with RHE plays an important role in the generation of tolerance against cerebral I/R injury, further studies are needed to clarify the mechanism of the ischemic tolerance.