Introduction: Plant long-chain isoprenoid alcohols (polyprenols) are biologically active molecules affecting the isoprenoid pathway. Polyprenols have broad therapeutic actions including for infections and inflammatory, hepatic and neurological conditions. The aim of this study was to evaluate the protective effects of pharmaceutical-grade polyprenols on experimental stroke in a mouse middle cerebral artery occlusion (MCAO) followed by reperfusion model. Methods: Pharmaceutical-grade polyprenol substance, Ropren®, is isolated from green verdure of ( Picea abies (L) Karst) . Adult (12-14 weeks old) C57BL/6 male mice were anesthetized (1.5% of isoflurane in 30% of O 2 and 70% of N 2 O) and body temperature was maintained (36.5-37.0°C) during 30-min filament-mediated MCAO and 48 h of reperfusion. Cerebral laser-Doppler flowmetry was utilized during MCAO to test whether regional cerebral blood flow (CBF) differences correlated with stroke outcome. Before and 24 h after MCAO, the experimental group was treated with Ropren® intraperitoneal injections (12 mg/kg) diluted in 100 μl sunflower oil. The control group was treated with 100 μl oil only at the same time points. Mice were euthanized 48 h after MCAO and infarct volumes were calculated (indirect method) after TTC staining. Results: Experimental stroke revealed a decrease in the cerebral infarct volume in the Ropren-treated group (51±16 mm 3 , Mean±SD) in comparison with the control group (67±13) (n=10/group, p < 0.05, two-tailed t-test). Neurological deficit measured by a 4-point scale was improved in Ropren-treated mice (1.2 points) compared with control mice (1.8) (n=10/group, p=0.05). We did not find a significant difference both between intra-ischemic CBF and CBF during reperfusion between groups (15th minute of reperfusion: 62±24% in Ropren-treated mice; 77±35% in control mice (n=10/group, NS)). This suggests Ropren® renders its neuroprotective effects by mechanisms independent of CBF. Conclusion: This study shows the protective effects of pharmaceutical-grade polyprenols (Ropren®) during cerebral ischemia-reperfusion injury in the mouse MCAO model. Further research is required to understand the mechanisms of Ropren-mediated neuroprotection in this ischemic stroke model.