Unregulated activation of microglia is the major cause of neuronal degeneration in Alzheimer's and Parkinson's diseases. Excessive reactive oxygen species (ROS) generation is a common risk factor for chronic diseases, including neurodegeneration. In this study, N-acetyl chitooligomers (NA-COS, below 1 and 1-3 kDa) were produced from crab chitin using an ultrafiltration-membrane system and investigated for their capabilities against H2O2-induced oxidative stress in murine microglia (BV-2 cells). NA-COS significantly decreased the oxidation of DNA by diminishing the intracellular ROS production. Furthermore, NA-COS upregulated the protein and gene expressions of antioxidant enzymes (superoxide dismutase and glutathione), thereby enhancing the intracellular antioxidant. Notably, NA-COS inhibit NF-kappa B activation by blocking degradation of the inhibitor of kappaB-alpha (I kappa B-alpha) and translocation of nuclear factor NF-kappa B (p65 and p50). Collectivefy, NA-COS could be potential agents for the prevention of neurodegenerative diseases. (C) 2016 Elsevier Ltd. All rights reserved.