Traumatic brain injury (TBI) induces complex secondary pathological processes, including neuroinflammation and intercellular communication within the injured brain microenvironment. Brain tissue-derived exosomes may provide information on local molecular alterations after injury, but their protein cargo changes after TBI remain incompletely characterized. In this project, brain tissue-derived exosomes were isolated from rats subjected to TBI or sham surgery and analyzed using label-free LC-MS/MS proteomics. The dataset includes five TBI samples and five sham control samples and was generated to identify injury-associated changes in exosomal protein cargo and provide a resource for exploring exosome-related molecular alterations during secondary brain injury.