Introduction: Obesity has been demonstrated to induce oxidative stress and inflammation processes that lead to senescence. Obesity-induced cellular senescence in the brain is still widely investigated. This study aimed to investigate the expression of senescence markers in the frontal lobes of obese rats. Methods: Three groups of rats: control, Obese-2 (Ob-2), and Obese-4 (Ob-4) were observed. Control rats were fed with a standard diet for one month. In contrast, Ob-2 and Ob-4 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 p-16, p-21, and beta-actin was performed to investigate the relative expression of the senescence markers. Results: Ob-2 and Ob-4 groups had significantly increased body weight after being fed with a high-fat diet for two and four months, respectively. The mRNA expressions of p-16 and p-21 in the frontal lobes of three groups showed similar patterns. The ob-4 group had the highest mRNA expressions of both p-16 and p-21. In comparison to control and Ob-2 groups, the mRNA expressions of p-16 and p-21 were markedly increased. Furthermore, the mRNA expressions of p-16 and p-21 between control and Ob-2 groups were comparable. Conclusion: Increased senescence markers in the rats’ frontal lobes were observed as the chronic effect of obesity.