Stroke remains a leading cause of adult disability in the United States. In recent studies, chronic vagus nerve stimulation (VNS) has been proven to enhance functional recovery when paired with motor rehabilitation training after stroke. Other studies have also demonstrated that delivering VNS during the onset of a stroke may elicit some neuroprotective effects as observed in remaining neural tissue and motor function. While these studies have demonstrated the benefits of VNS as a treatment or therapy in combatting stroke damage, the mechanisms responsible for these effects are still not well understood or known. The aim of this research was to further investigate the mechanisms underlying the efficacy of acute VNS treatment of stroke by observing the effect of VNS when applied after the onset of stroke. Animals were randomly assigned to three groups: Stroke animals received cortical ischemia (ET-1 injection), VNS+Stroke animals received acute VNS starting within 48 hours after cortical ischemia and continuing once per day for three days, or Control animals which received neither the injury nor stimulation. Results showed that stroke animals receiving acute VNS had smaller lesion volumes and larger motor cortical maps than those in the Stroke group. The results suggest VNS may confer neuroprotective effects when delivered within the first 96 hours of stroke.