We investigated the potential benefit of using a local infusion of low-dose and cold human albumin in ischemic rats as compared with systemic delivery.Stroke was induced in rats, and at 2 hours treatment groups received 0°C saline or low-dose albumin at 0°C or 37°C infused into the ischemic area.The local low-dose cold albumin infusion, which achieved the hypothermic temperature (P<0.001), produced the greatest reduction in infarct volume and the best recovery of neurological function.The local low-dose cold albumin infusion into the ischemic area offered a combination of regional brain hypothermia and albumin administration, which enhanced neuroprotection and would be beneficial in the clinical setting.