Abstract:The goal of these study was to evaluate the toxicity and severity of Zinc Oxide nanoparticle(ZnO-NPs) in gills tissue so Cyprinus carpio exposed to sub lethal concentration of ZnO-NPs 9mg/l for (7, 14, 21, 28, 35, 42) days cause histopathological and ultra structural alteration in gills tissue. Microscopic examination revealed hemorrhage and clup shape of epithelial cells that lining the secondary gill filament through (7 and 14 days of treatment), hyperplasia in mucus cells with hyper trophy of pillar cells at 28 days of treatment, and at day 42 the lesions were character by basement thickening in the secondary gill filament with edema and vacuolar degeneration of pillar cells. While ultra structural examination revealed presences cloudy swelling of chloride cells and condensation of micro organelles at 7 days of exposure ,the severity of lesions were increased with prolong time of exposure so at day 14 of exposure to ZnO-NPs the electron microscope examination exhibit thickening of blood vessels ,hyperplasia of mucus cells with vacuolar degeneration of chloride cells .Ultra structural changes in gills tissue of fish that exposed to N-ZnO for 42 days revealed microvilli and adhesion of micro ridge with degeneration of lining epithelial cells in the secondary gill filaments. In conclusion, ZnO-NPs are toxic in a concentration of 9mg/l in a common carp (Cyprinus carpio), that manifested by histopathological and ultra-structure alteration in gills and there was a positive relationship between the severity of lesions and time of exposure.