Abstract: Background　Traumatic brain injury (TBI), as a neurological disorder characterized by high disability and mortality rates, demands urgent innovation in therapeutic approaches. Although photobiomodulation (PBM) demonstrates potential as a novel non-invasive physical therapy, current research lacks systematic investigation into its mechanisms of action and efficacy parameters specifically for moderate traumatic brain injury. Objective　To investigate the neuroprotective effects and potential mechanisms of 1064 nm PBM in moderate TBI models.Methods　Thirty six 8-week-old male C57BL/6 mice were randomized into Sham group, TBI group, and PBM group. The TBI group and the PBM group were established using controlled cortical impact injury to model moderate brain injury, while the sham surgery group underwent identical craniotomy procedures without cortical impact induction. The PBM group received daily 1064 nm irradiation (25 mW/cm², 12 min/day) for 14 consecutive days. Behavioral assessments employing rotarod fatigue testing and Y-maze paradigms were implemented to quantify locomotor coordination and spatial working memory, while histopathological evaluation utilizing immunofluorescence staining on cryopreserved cerebral sections enabled quantitative analysis of glial fibrillary acidic protein (GFAP) astrogliosis and microtubule-associated protein 2 (MAP2) neuronal integrity, complemented by molecular profiling through quantitative real-time PCR (qRT-PCR) that systematically measured transcriptional alterations in brain-derived neurotrophic factor (BDNF) and astrocyte-mediated pro-inflammatory cytokines including tumor necrosis factor- α (TNF- α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) within peri-contusional parenchyma.Results　Rotarod test showed that the mean fall time was shortened following TBI and prolonged after PBM treatment. The mice in PBM group have a significantly longer distance of movement and a faster speed when falling relative to TBI mice (P < 0.05). The Y maze experiment showed that mice in the PBM group have an increase in the time and number of times to explore the new isometric arm relative to the TBI mice (P < 0.05). The expression of relative mRNA levels of BDNF in the brain tissues of the injury area in TBI mice was significantly lower than that in the Sham and PBM groups (P < 0.05). The mean fluorescence intensity of MAP2 in the brain tissue of the injury area in the TBI group was also significantly lower than that in the Sham and PBM groups, and the mean fluorescence intensity of GFAP was significantly higher than that in the Sham and PBM groups, with the differences being statistically significant (P < 0.05). In the vitro experiment, the expression of TNF- α, IL-1β and IL-6 in astrocytes was significantly decreased after PBM treatment, and the difference was statistically significant (P < 0.05).Conclusion　1064 nm PBM may improve motor and cognitive functions after moderate TBI by promoting the repair of neuronal damage, inhibiting the activation of astrocytes, as well as decreasing their levels of pro-inflammatory factors.