In this study, we examined the ameliorative action of N-Acetylcysteine (NAC) against Titanium Dioxide (TiO2) induced testicular degeneration in albino rats. Adult male albino rats were given saline as a control group, TiO2 (1200 mg kg −1 BW), NAC (100 mg kg −1 BW) and co-treatment of NAC and TiO2 as a protective group for 3 months. Testicular tissues were extracted for changes in testicular gene expression and histopathology. Administration of TiO2 significantly increased mRNA expression of IL-6 and TNF-α that are normalized by NAC administration. TiO2 administration down regulated Glutathione-S-Transferase (GST) while increased B-cell Lymphoma2 (BcL2) expressions. Co-administration of rats by NAC together with TiO2 normalized changes in GST and BcL2 expression. Expression of steroidogenesis related genes [Androgen Binding Protein (ABR), 17β-Hydroxysteroid Dehydrogenase (17β-HSD), cytochrome P450 17A (CYP17α) and aromatase] showed down regulation in TiO2 administered groups and normalized when NAC given together with TiO2. Moreover, TiO2 induced toxicity in testes that accompanied by degeneration in seminiferous tubules with congestion, oedema and cell disruption that are partially normalized by co-administration of NAC with TiO2. In conclusion, the present findings confirmed the benficial effect of NAC to prevent apoptosis of sertoli cells and testicular dysfunction induced by TiO2 in male albino rats.