Introduction: Increase in the consumption of nano zinc oxide in medicine, manufacturing cosmetic products, and in research has raised the questions about their toxicity.   Because of the small size of nano materials its absorption by the digestive system is simple. In this study, the effects of nano zinc oxide have been investigated in vivo on the ileum tissue of adult NMRI male mice.
 
Materials & Methods: In this experimental study, male mice were randomly divided into five groups, including control, sham, and three experimental groups. 10-30 nm-sized zinc oxide (ZnO) nanoparticles were injected intraperitoneally in three concentrations, 100-300-500mg/kg for 21 days. Histological changes including; height and width of the ileum villus, the thickness of the muscle tissue and epithelium tissue, width of connective tissue, diameter of crypts, and goblet cell numbers were studied by One Way ANOVA and Tukey-Kramer posttest, after treatments.
 
Findings: The results showed that nano zinc oxide had no effect on the height and the width of villi and diameter of crypts, but reduced the width of lamina propria and goblet cells of and increased the width of epithelium and muscle tissue ileum (P <0.05).
 
Discussion & Conclusions: The height and the width of villi and crypts diameter in the experimental groups had no significant difference compared to the sham and control groups. However, the width of the lamina propria and the number of goblet cells decreased significantly in all experimental groups, which indicated low toxicity of nano zinc oxide in these doses. A significant increase was observed in epithelium and muscle tissue compared to the control and sham groups. It seems that nano zinc oxide could be increase the growth of epithelial cells. Due to changes in the intestinal epithelium tissue in adjacent to nano zinc oxide, the long- term use of this material should be avoided.