Objective To explore the protective effect of 17β-estradiol on traumatic brain injury in rats. Methods A total of 45 adult male SD rats were divided into 3 groups using the random digit table, 15 rats in each group: the control group only exposed but not injured the brain, the injury group received traumatic brain injury (TBI) by Feeney's method, and the treatment group received the same handling with injury group, and pretreatment with 17β-estradiol peritoneal injection, 1 mg/kg per day for one week. The other two groups were given the same volume of castor oil. At 6 h, 24 h and 48 h after injury, the brain tissue water content, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured. Results At 6 h, 24 h and 48 h after injury, the levels of brain tissue water content in the injury group and treatment group were significantly higher than those in the control group (P<0.05). At 6 h after injury, the brain tissue water contents in the injury group and treatment group were (99.83±0.40)% and (99.53±0.41)%, respectively, with a non-significant difference between the two groups (P>0.05). At 24 h and 48 h after injury, the brain tissue water contents in the injury group was (105.17±0.43)% and (107.54±0.39)%, in the treatment group was (103.26±0.42)% and (105.89±0.43)%, respectively, showing a significant difference between the two groups (P<0.05). At 6 h after injury, the levels of MDA in the injury group and treatment group increased and maintained at a higher level, and the levels of SOD decreased. Compared with the control group, there had a significant difference (P<0.05). The levels of MDA and SOD in the injury group and treatment group at 6 h after injury had a non-significant difference (P>0.05). But at 24 h and 48 h after injury, the levels of MDA in the treatment group were significantly lower than those in the injury group [(130.39±7.02) μmol/g vs. (149.41±8.25) μmol/g, (125.41±6.59) μmol/g vs. (157.72±8.93) μmol/L], and the levels of SOD in the treatment group were significantly higher than thoset in the injury group [(88.46±7.17)U/g vs. (80.10±4.87)U/mg,(97.31±7.89)U/g vs. (84.29±6.13)U/g], with a significant difference (P<0.05) between the two groups. Conclusions 17β-estradiol has a protective effect on traumatic brain injury.