Objectives To investigate the effects of Nrf2-mediated antioxidant pathways on cognitive impairment and hippocampal neuronal damage in rats with vascular dementia. Methods A total of 30 adult male SD rats of SPF grade were developed models of vascular dementia. They were randomly divided into three groups： the control group， experiment group 1 and experiment Group 2. The control group was given an intravenous injection of 5 μl/d saline. experimental group 1 and experimental group 2 were given oxiracetam 10 ng/d and 100 ng/d intravenously for 2 weeks. The cognitive damage and hippocampal neuronal damage in rats were recorded， and the changes in Nrf2 expression and oxidative index were detected. Results There were no significant difference in escape latency across the three groups at 1 d after modeling（ P＞ 0.05）. The escape latency of the experimental groups at 7 d and 14 d after modeling was lower than that of the control group （P ＜ 0.05）； the the escape latency of experimental group 2 were lower than that of experimental group 1， but the difference was not statistically significant（ P＞ 0.05）. The activity of NADPH oxidase in the experimental groups was lower than that in the control group（ P＜0.05）； the activity of NADPH in experimental group 2 were significantly lower than experimental group 1（ P ＜ 0.05）. The relative expression levels of N-myc and Nrf2 proteins and the activity and survival rates of hippocampal neurons in the experimental groups were significantly higher than those in the control group（ P＜ 0.05）； those indicators of experimental group 2 were significantly higher than experimental group 1（ P＜ 0.05）. Conclusions Oxiracetam can ameliorate cognitive impairment and hippocampal neuronal damage in rats with vascular dementia， and its mechanism may be related to activation of Nrf2-mediated antioxidant pathways and N-myc-mediated neuronal growth pathway.