Background and Objective: Aging is a global, intrinsic, progressive, and damaging process that is associated with systemic inflammation, which is accompanied by the gradual accumulation of various injuries and a decrease in the functional efficiency and homeostasis of cells and tissues over time. Therefore, the aim of the present study was to investigate the effect of intense interval training on the levels of iNOS, COX-2, and Caspase3 proteins in the hippocampal tissue of aged Wistar rats. Research Methods: In this study, 30 male Wistar rats were prepared as samples in the aged groups with a weight of 480 grams and an age of 22 months and a young group with an age of 10 weeks and a weight of 190 grams, and after familiarization with the laboratory environment, they were randomly divided into three groups: control-young group, control-elderly group, and exercise-elderly group (each group of 10 rats). The training protocol for the HIIT group in the first week included treadmill running with a repetition rate of five two-minute intervals at an intensity of 80 to 100% of maximum speed. The training protocol included five sessions per week for six weeks. At the end of the sixth week, 48 hours after the last training session, the mice were anesthetized and their hippocampal tissue was extracted under sterile conditions and Western blotting was used to measure proteins. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Results: Aging significantly increased the expression of iNOS, COX-2, and Caspase3 genes in the hippocampal tissue of the brain (p<0.05). Also, following HIIT training, the expression of these genes decreased significantly (p<0.05). Conclusion: It seems that HIIT training can have a protective role in the hippocampus against the effects of aging by reducing factors involved in neuronal destruction.