Abstract: Objective To study the effects of α2A receptor agonists on cognitive function, inflammatory response and oxidative stress in elderly patients with brain tumor surgery, and to explore the possible mechanism of α2A receptor agonists on improving postoperative cognitive dysfunction in elderly patients with brain tumor surgery. Methods A total of 160 patients with brain tumor surgery from June 2013 to December 2017 treated in Wangjiangshan District of Zhejiang Provincial People's Hospital were selected, and were divided into the control group and the dexmedetomidine group according to the random number method, with 80 cases in each group. The dexmedetomidine group patients were preoperatively pumped with the α2A receptor agonist dexmedetomidine until the end of surgery. The MMSE scores were used to measure cognitive function of the patients. The serum IL-6 and TNF-α levels were determined by ELISA. The serum MDA concentration was determined by thiobarbituric acid staining. The serum SOD activity was measured by xanthine oxidase method. Results The incidence of postoperative cognitive dysfunction in the dexmedetomidine group (18.75%) was lower than that in the control group (38.75%, χ²=7.811, P=0.005). There were no significant differences in MMSE scores, serum IL-6 and TNF-α levels, serum MDA concentrations and SOD activities between the two groups before surgery (all P>0.05). After surgery, the MMSE score [(26.71±2.04) scores] and SOD activity [(88.42±8.74) U/mL] in the dexmedetomidine group were higher than those in the control group (all P<0.05), the serum IL-6 [(42.13±3.38) pg/mL], TNF-α levels [(16.27±1.95) pg/mL] and MDA concentrations [(5.14±1.27) nmol/mL] were lower than that in the control group (all P<0.05). Conclusion α2A receptor agonists improve postoperative cognitive dysfunction in elderly patients with brain tumor surgery by inhibiting inflammatory response and oxidative stress.