OBJECTIVE: Evidence suggests that exercise timing is crucial in reducing the impact of traumatic brain injury (TBI). The present study explores the effects of delayed and early exercise on brain damage, cognitive dysfunction, and anxiety behavior using an experimental TBI model. METHODS: We randomly assigned 36 male rats to six groups: control (sham, TBI), treadmill exercise (24hA, 1-month exercise 24 h after TBI), 1WA (1-month exercise 1 week after TBI), 1MB (1-month exercise before TBI), and 1MBA (1-month exercise before and after TBI). RESULTS: TBI caused significant impairments in cognitive and anxiety behaviors, as well as increased brain edema (p <
0.05). The exercise groups showed significant improvement in the following order for cognitive impairments: 1MBA >
24hA >
1WA >
1MB. Compared to the 1WA group, exercise starting 24 h after TBI (24hA) significantly improved all variables except anxiety behavior. Exercise 1MBA was significantly more effective than other groups (p <
0.05) in reducing cognitive problems, anxious behavior, and brain damage. CONCLUSION: Regular exercise or a consistent exercise routine before TBI, such as in athletes, may provide the most benefits from exercise intervention after the TBI. Starting exercise soon after the TBI (within 24 h) may help protect against brain edema and improve learning and memory by reducing cell death in specific brain regions (CA1 and CA3) and also decreasing TNF-α and MDA compared to starting exercise later (1 week after).