The aim of this study was to examine the adverse effects of zinc nanoparticles on hematological indices of trout and investigate the improvement of these indices after vitamin C treatments. This study assesses the protective role of vitamin C in fish exposed to ZnO NPs. Two concentrations of ZnO-NPs (40 and 80 mg L-1) and two doses of vitamin C (400 and 800 mg per kg of feed) were used to treat 162 specimens of Oncorhynchus mykiss. No mortality was observed during the test. After 5 and 10 days of exposure, hematological data were analyzed according to routine clinical methods. Statistical analysis showed significant changes in WBCs and RBC on day 10 (p < /em><0.05). Values for HT and MCH were significantly higher in treatment 2 (normal diet+40 mg L-1 ZnO-NPs) and 9 (800 mg/kg Vit + 80 mg L-1 ZnO-NPs), and lower in treatment 3 (normal diet+80 mg L-1 ZnO-NPs) in comparison with the control group (normal diet+0 mg L-1 ZnO-NPs) (P < /em><0.05). No significant differences of MCV and MCHC were observed (p < /em>>0.05), while significant increase in neutrophils and monocytes, and decrease in lymphocyte cells were recorded (p < /em><0.05). ZnO-NPs stimulated the immune system of O. mykiss, but this effect did not have any lethality on this species at 40 and 80 mg L-1. Vitamin C in different concentrations could help to prevent rainbow trout from the toxic effects of this nano metal.