Platelet-rich plasma (PRP) is a milieu of bioactive factors, including platelet derived growth factor, transforming growth factor beta, among many others. Despite accumulating evidence on PRP's safety and efficacy for treating musculoskeletal injuries, limited studies have been performed using PRP in brain disorders. This study aimed to explore the potential benefits of administration of human PRP lysate after ischemic stroke in rats. An ischemic stroke model was generated by occlusion of the right middle cerebral artery, then 90 min later, stroke rats were randomly assigned to receive local infusion to the ischemic area of human PRP lysate, human albumin solution (HSA), saline or no treatment at all. An additional group of stroke rats received systemic infusion of human PRP lysate to further assess the therapeutic effects of this treatment. Results showed that while local infusion of HSA or saline, and systemic administration of human PRP lysate, compared to no treatment significantly reduced infarct volume (37.4%, 40.1%, and 39.9% vs 49.7%) and neurological deficit score (2.2, 2.6, and 2.8 vs 3.7), the greatest neuroprotection (31.0% infarct volume and 1.6 neurological deficit score) was found in stroke animals that received local intra-arterial infusion of human PRP lysate (p's<0.05). In conclusion, administration of human PRP attenuates brain injury after focal ischemia. Our results suggest PRP should be investigated further as a potential point-of-care biomaterial following stroke.