Objective To explore the effects of dexmedetomidine on the level of endothelin-1 in blood samples of patients with serious brain injury. Methods Fourty patients with serious brain injury were assigned to 2 groups randomly (n=20 each): dexmedetomidine group (group D) and control group(group C). The level of endothelin-1 (ET-1) in blood samples was measured in the following time point, before induction of anesthesia(T0), after tracheal intubation(T1), after operation(T2), as well as on the 1st day, 3rd day and 5th day after operation (T3, T4, T5), and the hemodynamic parameters at these time points were recorded. Results Compared with T0, HR increased significantly at T1, and HR, MAP as well as plasma ET1 decreased at T3 in C group. And compared with T0 in D group, HR and MAP is lower at T1-5 than T0, while the plasma ET1 decreased siginificantly at T2-5. HR and MAP at T1~3, plasma ET-1 at T2~5 were significantly different between the two groups （P<0.05）. One of patient in group C die of neurogenic pulmonary edema. Conclusions Continued application of dexmedetomidine cause a decrease in the level of ET-1 and play a role in maintaining hemodynamic stability.