Deferoxamine (DFO) is a metal chelator found to decrease cognitive decline in a clinical trial of Alzheimer’s patients. However, this trial included painful intramuscular injections and side-effects. Recent studies have shown that when delivered intranasally, DFO decreased memory loss in the APP/PS1 (amyloid) and P301L (tau) mouse models of Alzheimer’s disease (AD). Here, normal C57 mice, the background strain of both models, were treated with intranasal (IN) DFO to determine whether memory might be improved from baseline. Treatment groups (n=14) consisted of IN DFO, IN saline (control: IN delivery), intraperitoneal (IP) DFO (control: peripheral vs central effects), and IP saline (control: IP delivery). Mice were treated five days/week for four weeks with 2.4 mg DFO or saline. Mice performed daily behavior tests beginning 30 min. after dosing. At the end of four weeks mice were euthanized and brain tissues analyzed. Intranasal DFO significantly improved memory in the Morris and radial arm water maze (p<0.05), whereas treatment with IP DFO did not. No differences were detected in other behavior tests. Brain tissues of mice treated with IN DFO yielded a significant decrease in activity of GSK3â, a kinase that plays a significant role in AD. Oxidative stress was also decreased in mice treated with IN DFO. These results demonstrate that IN DFO improves memory in normal mice. The fact that IN DFO improved memory and IP DFO did not suggests that targeting to the brain may be beneficial and suggests that IN DFO has potential for the treatment of AD.