These results demonstrated that repeated exposure to CPF can induce PD via apoptotic cell death, histopathological disruption. Furthermore, the numbers of apoptosis cells reduced in substantia nigra ( P < 0.001) after the 30-day period of CPF injections. Additionally, in substantia nigra, the expression of GFAP had a significant increase and the TH had a remarkable decrease in CPF injected group in comparison to two other groups ( P < 0.001). normal and sham groups significantly ( P < 0.001). Moreover, results indicated that the proportion of neurons decreased in the second group vs. The results witnessed an increase in MDA and a decrease in SOD ( P < 0.05) after the CPF treating. Finally, the expression of GFAP and TH was investigated in the brain of animals. Proportion of neurons was analyzed by crystal violet assays and tunnel assay to detect apoptotic cells. At the end of the CPF treatment, malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured in the brain tissues of rats. The first group was normal control which the animals did not received any treatment, while in the second group, CPF were injected (CPF 5 mg/kg BW for 30 days intraperitoneally) and the sham group as the third group received DMSO. 6 to 8-week-old animals were categorized into three groups. The aim of this study was to evaluate the effect of CPF on inducing the Parkinson’s disease affecting on central nervous system. CPF has detrimental effects on brain tissue, so it is possible to generate some neurodegenerative diseases. Chlorpyrifos (CPF) is one of the most abundant and widely used pesticides in the world.