Objectives Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Neuritin is a neurotrophic factor that regulates neural growth and development. However, the role of neuritin in alleviating TBI has not been investigated. Methods In this study, Sprague Dawley rats (n = 144) weighing 300 ± 50 g were categorized into control, sham, TBI, and TBI + neuritin groups. The neurological scores and the ultrastructure of cortical neurons, apoptotic cells, and caspase-3 were measured by using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, Western blot analysis, and real-time RT-PCR at various time points post-TBI. Conclusions Our findings indicated that neuritin plays a protective role in TBI by improving neurological scores, repairing injured neurons, and protecting the cortical neurons against apoptosis through inhibition of caspase-3 expression. Further investigation of the molecular mechanisms underlying caspase-3 inhibition by neuritin will provide a research avenue for potential TBI therapeutics.