Objective To investigate the neuroprotective effect of the α₂ adrenergic agonist dexmedetomidine in rat brain tissues after traumatic brain injury by assessing expression of nuclear factor kappa B, tumor necrosis factor α (TNF-α), and interleukiN-1β ( IL-1β). Methods Male Sprague-Dawley rats were randomly divided into one of three groups: the sham operation group ( group S ), the cerebral ischemia-reperfusion group ( group C ), and the dexmedetomidine group (group D). Each of these groups was then subdivided into subgroups of 6 rats each for time points 2, 6, 12, 24, and 48 h. Parietal brain contusions were induced according to a modified Longa method. The rats in group S then underwent a sham operation. For group D, 2 h after successful embolization a wire was pulled into the stump of the external carotid artery to simulate ischemia and reperfusion, and 30 min later the rats received an intraperitoneal injection of the α₂ adrenergic receptor(α₂ -AR)agonist dexmedetomidine at a dose of 100 μg / kg (4 μg / mL). Group C underwent the same procedure as group S, but 0. 9% NaCl was injected instead of dexmedetomidine. At each time point, nuclear factor kappa B expression was detected using western blotting, and TNF-α and IL-1β expression were detected using ELISA. Six rats were selected for scoring of neurological deficits at 24 and 48 hours after model preparation, including test response, alertness, and coordination. Six rats were selected 24 and 48 hours after model preparation and randomly placed facing the wall in one quadrant of a cage with a central platform, and, the time it took to find the platform within 60 s was recorded. If the platform was not found within 90 s, the escape latency was recorded as 90 s. Five times were recorded and the average value was calculated. Results No significant differences in TNF-α and IL-1β expression in the brain tissue at 6, 12, 24, and 48 h in group S were found. TNF-α and IL-1β expression was higher in group C than in group S (P <0. 05), higher in group D than in group S (P <0. 05), but lower in group D than in group C (P <0. 05). At 24 and 48 hours after model preparation, compared with group S, neurological deficit scores were higher in groups C and D (P <0. 05), and escape latency was prolonged ( P < 0. 05). Neurological deficit scores were higher in group D than in group C ( P < 0. 05). Conclusions The α₂ adrenergic agonist dexmedetomidine protects brain tissue by inhibiting the inflammation induced by cerebral ischemia-reperfusion in rats.