Fipronil (FIP) is a globally utilized insecticide that leads to environmental pollution. Exposure of non-target organisms to FIP causes occupational and non-occupational neurological hazard. Therefore, this study aimed to assess the histopathological and immunohistochemical changes in the cerebral cortex of adult albino rats exposed to FIP. Twenty adult male albino rats were divided into 2 groups: control and experimental groups. Each rat of the experimental group received a daily oral dose of FIP at 10 mg /kg body weight. After 45 days of FIP daily administration, samples from the cerebral cortex were collected from both groups and were processed for histopathological and immunohistochemical examination. The cerebral cortex of treated rats showed severe neuronal degeneration, reactive gliosis, neuropil vacuolation and elevated immunoreactivity to GFAP, iNOS and Caspase 3 (active form). In conclusion, sub-acute FIP exposure has neurotoxic effect that appeared in our study in the form of apoptosis and tissue reactivity of the cerebral cortex.