Perfluorooctanoic acid (PFOA) is a member of Per- and polyfluoroalkyl substances (PFASs), an industrial pollutant that has been produced for decades and widely used in various industries. Accumulation of this compound in the environment and body of organisms led to increased concerns about this compound. The toxic effects of PFOA on the nervous system are unknown yet. We aimed to assess the myelination and neurogenesis in brain tissue. In this study, PFOA at doses of 1, 5, 10, and 20 mg/kg were injected intraperitoneally into C57BL/6 J mice for 14 days, and the myelin content, CD4 + and CD8 + cell infiltration to brain regions were evaluated. Also, bromodeoxyuridine (BrdU) labeling was performed to compare neurogenesis among the groups. Luxol Fast Blue (LFB) staining revealed a significant decrease in myelin content in both sex at high concentrations (p < 0.001). The BrdU incorporation changes were observed in both sexes especially females which was highly related to the dose of PFOA and region of the brain. The infiltration rates of CD4 + and CD8 + cells to the brain were shown to be decreased; meanwhile the lymphocyte count was not significantly changed among groups over time and vice versa for the monocyte and neutrophils. Our results showed that PFOA had a negative impact on neurogenesis and the myelination process through the specific region of the brain depending on the dose and sex. Also, PFOA could disturb the number of CD4 + and CD8 + cells infiltrating the brain, which plays a crucial role in neurogenesis, leading to toxicity and neurological abnormalities. It seems that more research is needed to determine the exact mechanisms of PFOA neurotoxicity and its long-term behavioral consequences.