The deduced amino acid sequences from the complete cDNA coding sequences of three antioxidant enzyme genes (cm sod1 , cm sod2, and cm cat ) demonstrated that phylogenetically the magur catfish ( Clarias magur ) is very much close to other bony fishes with complete conservation of active site residues among piscine, amphibian and mammalian species. The three-dimensional structures of three antioxidant enzyme proteins are very much similar to mammalian counterparts, thereby suggesting the functional similarities of these enzymes. Exposure to ZnO NPs resulted in an oxidative stress as evidenced by an initial sharp rise of intracellular concentrations of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA), but decreased gradually at later stages. The level of glutathione (GSH) also increased gradually in all the tissues examined after an initial decrease. Biochemical and gene expression analyses indicated that the magur catfish has the ability to defend the ZnO NP-induced oxidative stress by inducing the SOD/CAT enzyme system and also the GSH-related enzymes that are mediated through the activation of various antioxidant-related genes both at the transcriptional and translational levels in various tissues. Furthermore, it appeared that the stimulation of NO, as a consequence of induction nos2 gene, under NP-induced oxidative stress serves as a modulator to induce the SOD/CAT system in various tissues of magur catfish as an antioxidant strategy. Thus, it can be contemplated that the magur catfish possesses a very efficient antioxidant defensive mechanisms to defend against the oxidative stress during exposure to ZnO NPs into their natural environment, and also from related cellular damages.