Background: Nanosilver (NS) contains silver nanoparticles to control infections delivered from bacteria. The NS compounds as well as being toxic to prokaryotes are highly toxic to mammalian cells. The present study was evaluated the effect of colloidal NS on leydig cells glucose transporter type I (GLUT I) expression, serum level of testosterone, germinal cells RNA damage and spermiogenesis process.Materials and Methods: Twenty four mature male mice were divided into four groups (n=6) as test and control sham groups. The animals in test groups received the colloid NS in doses of 0.5, 1 and 5 mg/kg and the animals in control-sham group received saline intraperitoneally, during 34 consecutive days. The immunohistochemical and Epi-fluorescent analyses were conducted to evaluate the GLUT I expression and germinal cells RNA damage, respectively. The serum testosterone level was assessed by RIA method. The spermiogenesis index was investigated.Results: The GLUT I expression significantly (p<0.05) decreased in NS-administrated animals. Accordingly, the high dose received mice were manifested with lowest GLUT I on leydig cells. The serum level of testosterone decreased depending on dose. The germinal cells were exhibited with severe RNA damage accomplished with remarkable reduction in the percentage of seminiferous tubules with positive spermiogenesis index.Conclusion: Our data suggest that NS partly by reducing GLUT I expression on the leydig cells membrane down-regulates the cells glucose intake. Therefore, the leydig cells loss their physiologic ability to synthesis testosterone. Ultimately, the induced impairment leads to severe RNA damage in germinal cells which negatively impacts the spermiogenesis process.