Reactive oxygen species (ROS), generated during the metabolism process in all of the oxygen-utilizing organisms, damaged to proteins, lipids, and nucleic acids, contributed to the oxidative stress and aging related neurodegeneration. Peroxiredoxin II (Prx II), as the antioxidant enzyme has been known to play an important protective role against oxidative damage of ROS. To define the possible roles of Prx II in central nervous system, we investigated the Prx II function in vitro and in vivo using Prx II -/- mice.In primary cortical neuron culture, we found that Prx II -/- neurons rapidly degenerated only in antioxidants deficient culture condition. This cell death was apoptosis, and can’t be prevented by caspase inhibitor. The mitochondria membrane potential decreased in Prx II -/- neurons, when almost all neuronal cells’ m collapse, the Prx II -/- neurons degenerated. So, Prx II -/- neuronal cell death induced by oxidative stress was mediated by mitochondria. In vivo results showed that LTP was decreased in Prx II -/- mice in age dependent manner. And behavior tests results also proved the deficits of aged Prx II -/- mice in learning and memory. The molecular base of these disabilities, maybe due to the mitochondria. Decreased quantity of mitochondria, and abnormality of mitochondria, was very predominant in the aged Prx II -/- mice brain. And the anatomical base of synapse: spines, was greatly decreased in the aged Prx II -/- dendrites.Here we presented that Prx II play an important role in central nervous system. In our knowledge, it was the first report of Prx II function in neuronal cells in vitro, and in vivo. Since mitochondria have a central role in aging related neurodegeneration diseases. The findings in this study suggested that Prx II is an important clinic therapeutic target in mitochondria associated neurodegenerative disease.