Stem cell-based therapy shows great potential in stroke patients. Intra-artery infusion exhibits greater biological distribution compared to intravenous delivery. In addition, umbilical cord mesenchymal stem cells (UCMSCs) have several advantages compared with other types of stem cells. The aim of this study was to evaluate the safety and efficacy of UCMSCs delivered by a catheter to a near lesion site for treatment of an infarction in the middle cerebral artery territory. Four patients with stroke (three with ischemic and one with hemorrhagic stroke) in the middle cerebral artery territory were recruited in this study. One single dose of 2 × 10(7) UCMSCs was infused within 20 min via catheterization in the M1 segment of the middle cerebral artery. The safety and efficacy of this approach were assessed during the in-hospital and 6-month follow-up evaluation. The cell delivery was successfully performed in all of the patients, and no major accidents (stroke or death) were observed. Moreover, no fever or rash was reported. After cellular therapy, two of the three ischemic stroke patients demonstrated improved muscle strength. The improvement of the modified Rankin scale was observed in two patients, both of whom suffered from ischemic stroke at 90 and 180 days after the stem cell therapy. The hemorrhagic stroke patient failed to demonstrate improved muscle strength and did not amend his daily activities. Intra-artery delivery of UCMSCs via catheterization was a feasible and safe approach and may improve the neurological function of ischemic stroke patients with the middle cerebral artery territory infarcts.