Nano-size zinc oxide particles (ZnO NPs) are used in diverse industrial and commercial fields. However, the information from existing studies is not sufficient in evaluating the potential toxic effects of ZnO NPs. In this study, tilapia fish (Oreochromis niloticus) were exposed to different concentrations of small and large ZnO NPs in vivo. Accumulation in various organs/tissues (liver, gill, intestine, kidney, brain and muscle) and possible oxidative stress mechanisms were investigated comparatively. Fish were exposed to 1 and 10 mg/L concentrations of small (10-30 nm) and large (100 nm) ZnO NPs semi-statically for 14 days. Both small and large ZnO NPs accumulated substantially in the tissues. Accumulation for the small ZnO NPs was significantly higher compared to larger NPs under same exposure regimes. Significant fluctuations were observed in antioxidant defense system biomarkers, including Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) levels depending on particle size, exposure time and concentration. Lipid peroxidation measured with TBARS levels were higher in groups exposed to the suspensions of small ZnO NPs than that of large ZnO NPs and controls. These results imply that colloidal suspensions of small ZnO NPs induce elevated oxidative stress and toxic effects on tilapia compared to the larger NPs. (C) 2015 Elsevier B.V. All rights reserved.