Introduction: Obesity has been demonstrated to induce oxidative stress and inflammation processes that lead to senescence in brain cells. Obesity-induced cellular senescence in the brain is still widely investigated. This study aimed to investigate the expression of antioxidant and neuronal markers in the frontal lobes of obese rats. Methods: Eighteen adult rat Sprague Dawley divided into three groups: Control (SO), Obese-2 (DIO2), and Obese-4 (DIO4) were observed. Control rats were fed with a standard diet AIN 76A for two month. In contrast, DIO2 and DIO4 rats were fed with a high-fat diet daily for two and four months, respectively. After being sacrificed, the rats’ brains were dissected out then the frontal lobes were used for RNA extraction. Reverse transcriptase PCR of SOD2, GPx, BDNF, NeuN and beta-actin was performed to investigate the relative expression of the antioxidant and neuronal markers. Results: DIO2 and DIO4 groups had significantly increased body Weights, blood glucose level and triglyceride level after being fed with a high-fat diet for two and four months, respectively. The DIO4 group had the significantly lowest mRNA expressions of SOD2, GPx, BDNF and NeuN. Conclusion: Decreased antioxidant and neuronal markers in the rats frontal lobes were observed as the chronic effect of obesity.