Stroke is the second most common cause of death and major cause of disability worldwide. Actual treatment involves surgery and/or thrombolytic drugs, but there is an urgent need for new approaches. Periodic acceleration, a rocking headward to footward movement of the whole body, is a non-invasive method to induce pulsatile shear stress on the vascular endothelium eliciting an enhanced production and secretion of endothelium-derived products such as nitric oxide, prostacyclin, prostaglandin E2, tissue plasminogen activator (tPA), and adrenomedullin. All these products have been shown to protect the brain from ischemic injuries. A rat model of focal brain ischemia was treated with application of periodic acceleration for 3 h immediately after the onset of ischemia. Controls remained static for the same period of time. Brain damage was assessed by magnetic resonance imaging (MRI) and biochemical markers. A significant reduction in brain damage was observed, 7 days post-ischemia, in rocked rats when compared with the static controls, through MRI. Furthermore, rocked animals had significantly lower levels of Beclin 1 and fractin than their static counterparts, and some isoforms of nitric oxide synthase were regulated by periodic acceleration. Our results show that periodic acceleration may provide a novel, affordable, non-invasive therapeutic option for the treatment of stroke.