Background and purpose: Human Placenta-Derived Adherent cells (PDAC TM ) are a novel adherent mesenchymal-like cell population derived from normal, full-term human placental tissue. PDA-001 (cenplacel-L) is a clinical formulation of PDAC TM developed for intravenous administration. In this study, we investigated the efficacy of PDA-001 treatment in a rat model of transient middle cerebral artery occlusion (MCAo) in older-adult rats. Methods: Older-adult male Wistar rats (600-750g, 10-12 months) were subjected to 90 minutes of MCAo. To test the efficacy of PDA-001 treatment in older-adult rats, at 1 day after MCAo, randomly selected animals (n=12 per group) were injected, via a tail vein, with vehicle control (cell media), or with PDA-001 (4x10 6 or 8x10 6 cells). Treatment response was evaluated using a battery of functional outcome tests, consisting of adhesive-removal test, modified Neurological Severity Score (mNSS) and foot-fault test. All rats were sacrificed 29 days after MCAo, and lesion volumes were measured using hematoxylin and eosin (H&E). To assess cerebral tissue for angiogenesis and synaptogenesis, immunohistochemical stainings for bromodeoxyuridine (BrdU) and von Willebrand Factor (vWF), and synaptophysin were performed, respectively. Results: PDA-001 treatment at the 4X10 6 and 8X10 6 doses significantly improved functional outcome after stroke in older-adult rats (p<0.05). The neurological benefit of PDA-001 treatment was associated with significant increases in the number of BrdU immunoreactive endothelial cells, increases in vascular density and perimeter in the ischemic brain (p<0.05), as well as significantly increased synaptic plasticity as measured by increased synaptophysin expression in the ischemic border zone (IBZ) (p<0.05). Conclusion: PDA-001 treatment significantly improved functional outcome after stroke in older-adult rats. The neurorestorative effects induced by PDA-001 treatment may be related to the increase in angiogenesis and synaptic plasticity.