Objective To investigate the changes of content or activity of Nrf2 and anti-oxidative stress-related factors in rat models of traumatic brain injury, and explore the mechanisms of protective effect of curcumin on brain damage and oxidative stress in rats. Methods Twenty healthy SPF male SD rats were divided into 4 groups: the control group, brain injury model group (TBI group), brain injury and solvent-treated group (TBI + S group), brain injury and curcumin-treated group (TBI + C group), 5 rats ineach group. The control group received only saline and anesthesia. The TBI, TBI + S and TBI + C groups were given free falling body brain injury modeling device to establish the models and then received curcumin (5 mg/ kg), an equal amount of DMSO solvent (0.05%) and an equal amount of physiological saline, respectively. The rats were sacrificed at the next day and the RNA and proteins of brain tissues were extracted. qRT-PCR and Western blot were used to detect the mRNA and protein expression of Nrf2. Chemocolorimetry was used to detect the content or activity of MDA, GSH, CAT and SOD in the brain tissues of rats. ELISA was used to detect the contents of iNOS and HO-1. Results Compared with the control group,the mRNA and protein expressions of Nrf2, the content of MDA,the activity of HO-1 and iNOS were significantly increased, the content of GSH, the activity of SOD and CAT were significantly decreased in the TBI group and TBI + S group, with a significant difference ( P < 0.05). Compared with the TBI and TBI + S groups, the mRNA and protein expressions of Nrf2, the content of MDA, the activities of HO-1 and iNOS were significantly decreased, the content of GSH, the activity of SOD and CAT were significantly increased in the TBI + C group, showing a sigfnificant difference ( P < 0.05), but there were no significant differences between the TBI group and TBI + S group ( P < 0.05). Conclusions Curcumin has an anti?oxidative stress effect on rats with brain injury. It can reduce the expression of Nrf2, change the anti?oxidant stress?related indicators, therefore to protect the TBI?impaired brain tissues.