Background and Objective:In neurodegenerative disorders, oxidative stress mediated by reactive oxygen species is strongly associated with increased neuronal damages that lead to apoptosis. Pro-apoptotic and anti-apoptotic gene expressions were changed during cell differentiation that affect cell viability and differentiation. This study was conducted to determine the effects of hydrogen peroxide-induced oxidative stress on apoptotic cell death in the differentiated rat pheochromocytoma (PC12) cells. Materials and Methods: Semi-differentiated PC12 cells were treated with 400 µM hydrogen peroxide. Characteristic morphological changes as anapoptotic index were evaluated by DAPI staining. MTT assay were used to evaluate cells survival and activity. Pro-apoptotic and anti-apoptotic gene expression were estimated by real time-PCR. Results: The obtained data indicate that PC12 cell survival rate decreases in H2O2-treated condition during differentiation. Also, H2O2 increases apoptotic genes expressions including caspase 6 and PIN1 and decreases anti-apoptotic genes including sirt1 and sirt7. Conclusion: H2O2-induced oxidative stress can retard the differentiation of PC12 cell to neural-like cells through the apoptotic gene expression. On the other hand, despite the PIN1 acts as an apoptotic gene, this study illustrated that the expression of this gene is increased during differentiation under oxidative stress conditions.