Background and Objective: With the increase in the production of nanoparticles, human beings are exposed to its potential dangers. Research has shown the antioxidant effects of zinc oxide at low doses, but long-term exposure to high doses has pro-oxidant effects and influences the function of the male reproductive system, spermatogenesis and fertility. The present study was conducted to investigate the effect of N-acetyl cysteine on testicular tissue changes and spermatogenesis process in male mice treated with zinc oxide nanoparticles. Methods: In this experimental study, 24 adult male mice were assigned to groups of control (1 ml/kg saline), zinc oxide nanoparticles (50 mg/kg), N-acetyl cysteine (150 mg/kg) and N-acetyl cysteine + zinc oxide nanoparticles. In all groups, intraperitoneal injections were performed daily for 28 days. At the end of the treatment, mean weight and volume of testicles, length and diameter of seminiferous tubules, height of germinal epithelium and number of germ cells were evaluated. Findings: In the group of zinc oxide nanoparticles, a significant decrease was observed in volume (38.86±1.48), length (0.89±0.09), diameter (162.69±1.03), and height of germinal epithelium (41.06±1.73) of the seminiferous tubules, number of spermatogonia (4.15±0.11) ×106 , spermatocytes (21.45±0.83) ×106 , round spermatid (22.31±0.47) ×106 , elongated spermatid (21.74±0.76) ×106 and Sertoli cell (3.08±0.10) ×106 and a significant increase was observed in interstitial tissue volume (18.04±1.84) compared to the control group (p<0.001). In the concurrent treatment group, N-acetyl cysteine improved the above parameters compared to the group of zinc oxide nanoparticles (p<0.01). These parameters were not significantly different in the N-acetyl cysteine group compared to the control group. Conclusion: Based on the results of this study, N-acetyl cysteine was able to prevent the damage caused by zinc oxide nanoparticles on testicular tissue and spermatogenesis
