Aims: Post-injury physical exercise can reduce memory deficits associated to traumatic brain injury (TBI) in late adolescent and young adult rats, but both the effectiveness of this treatment and possible sex-dependent effects in late middle-aged injured rats are important issues still unsolved. The aim of the present work was to examine whether chronic object recognition memory (ORM) deficits associated to TBI can be alleviated by post-injury physical exercise in males and females late middle-aged rats. Methods: 14 months-old rats were submitted to a controlled cortical impact injury model of TBI. Starting one week after surgery, half of the animals had continuous access to a running wheel along 7 weeks, while the remaining half were maintained in a sedentary condition. Training in the ORM task was done during the last week of exercise treatment. Results: TBI impaired the performance of an hippocampal-dependent variant of ORM in both males and females. Despite male rats exhibited significantly lower daily exercise levels than females, this low exercise amount was effective to attenuate the memory deficits. In contrast, exercise intervention did not show positive effects in females. Conclusions: The benefits of physical exercise on ORM in late middle-aged rats exposed to TBI are sex dependent. Immunohistochemistry and proteomic analyses are currently in progress to determine whether this sex-dependent cognitive effect can be attributed to differences in the neuroinflammatory processes and/or in the muscle-to-brain crosstalk.