Background and purpose: ZnO nanoparticles are able to produce changes in intracellular calcium, the expression of transcription factors and cytokines by producing reactive oxygen species (ROS) and lead to changes in the transcription process of genes, damaging cell DNA and apoptosis. The aim of this study was to investigate the antioxidant effect of N-acetylcysteine on testicular tissue changes, spermatogenesis and daily sperm production in mice poisoned with zinc oxide nanoparticles. Materials and methods: In this study, 24 adult male NMRI mice (37±2gr) were randomly divided into four groups (n=6): control group (saline, 1 ml/kg), group treated with Zno NPs (50mg/kg/day), group treated with N-acetylcysteine (150mg/kg/day) and group treated with N-acetylcysteine (150mg/kg/day) + Zno NPs (50mg/kg/day). After 28 days of intraperitoneal treatments, the left testis was removed and after fixation, sectioning, tissue processing and staining with Hematoxylin and eosin method, was evaluated stereologically. Data were analyzed using one way ANOVA and the means were considered significantly different at )P<0.05(. Results: In zinc oxide nanoparticles group a significant decrease in the volume, length, diameter and height of the germinal epithelium and a significant increase in the interstitial tissue of the seminiferous tubules compared to the control group was observed (p<0.001) also in this group the mean number of spermatogonia, spermatocytes, round and long spermatid and Sertoli cells compared to the control group showed a significant decrease (p<0.001). In Co-treatment group N-acetylcysteine improved the above parameters compared to the group of zinc oxide nanoparticles (p<0.01). These parameters were not significantly different in the N-acetylcysteine group compared to the control group (p>0.05). Conclusion: N-acetylcysteine as a powerful antioxidant by increasing the amount of glutathione is able to neutralize free radicals and by preventing the formation of proinflamma
