This study was conducted to investigate the toxic effect of Fe2O3 nanoparticles on the histological changes of the vital organs of male mice. The iron oxide nanomaterials were prepared by chemical method; several doses of it were used at different concentrations, which are 12, 10, 8, 6%. The dose is administered to the mice orally every 48 hours for a period of 60 days. The mice were divided into 6 groups in addition to the control group during the mentioned period; weights were taken for all groups throughout the experiment period. After the completion of the experimental period, the mice of all the mentioned groups were killed. The results of the histological examination with the first and second concentrations did not show any toxic effects or changes in the functional structures of the mentioned organs. while slight changes appeared in the high concentrations of nanoparticles, as it was found that there was some blood congestion and inflammation in the kidneys. There is also congestion in parts of the liver with enlargement in some cells, as well as congestion in the brain, at concentrations of 12.10%. While no structural changes appeared in the first and second concentrations, also in the control group, no changes appeared in the functional structure of the above members. From the results of the study, we conclude that the use of high concentrations of nanoparticles of iron oxide may lead to changes in the functional structures of the kidneys, liver and brain, and may lead to toxic effects on the rest of the body.