In recent years, with the widespread use of zinc oxide (ZnO) nanoparticles (NPs), more and more attentions are being given to its biological toxicity, the toxicity of ZnO NPs under different exposure methods is necessary to investigate. In this study, we prepared two ZnO dispersions with different particle sizes, namely small-size ZnO (S-ZnO) and Big -size ZnO (B-ZnO), using polycarboxylic acid as dispersant. Mice were poisoned by intravenous injection and inhalation, respectively. The respiration coefficient, superoxide dismutase (SOD), Zn content in the organs of the mice were detected. It was discovered that ZnO NPs with smaller particle diameter can cause more serious toxicity in vivo after intravenous exposure and respiratory exposure. In addition, the mice showed symptoms of dyspnea after respiratory exposure and a massive number of fibroblasts were found in the alveolar structure of the lungs. In the intravenous injection group, the content of Zn in the liver and spleen of mice increased significantly, resulting in organ edema, and the organ coefficient of mice increased. Finally, the increase of GSH/GSSG indicated that cells were regulated under the antioxidant mechanism, which accelerated the removal of H2O2 from cells. In addition, the increase of GSH+GSSG content also indicated that IP 846247 10 O M n, 31 O t 2022 0805 16 ZnO NPs stimulated the creation of reactive oxygen species (ROS) in organs of experimental animals. Copyright: American Scientifc Publshers