The aim of this study was to investigate the effect of ceftriaxone treatment against short-term global brain ischemia/reperfusion (I/R) injury in rats. The study was carried out on 30 Wistar-albino rats that were divided into three groups: control group (n = 10), I/R group (n = 10) and I/R-ceftriaxone group (n = 10). Malondialdehyde (MDA) levels were significantly increased in the I/R group in comparison with the control group (p < 0.001). MDA was significantly lower in the I/R-ceftriaxone group than in the I/R group (p < 0.05). Superoxide dismutase activity was significantly decreased in the I/R group and increased in the I/R-ceftriaxone group as compared with the control group. Glutathione peroxidase activity was significantly decreased in the I/R group and increased in the I/R-ceftriaxone group as compared with the I/R group and the control. Histopathologically, ceftriaxone provided morphological improvement compared with the I/R group. We concluded that ceftriaxone has neuron-protective effects due to its antioxidant properties as shown by a decrease in MDA overproduction and histological improvement in brain tissue. (C) 2012 Elsevier Ltd. All rights reserved.