Objective: To investigate the effect of dexmedetomidine on postoperative lung injury in patients undergoing thoracoscopic surgery. Methods: From March 2019 to October 2019, 40 patients were randomly divided into two groups: dexmedetomidine group (group D) and control group (group C). Except recording the general condition of the patients in both groups preoperatively and intraoperatively, the oxygenation index (OI) and alveolar-arterial oxygen partial pressure difference (A-aDO2) were monitored at admission (T0), immediately after one-lung ventilation (T1), 0.5 h after one-lung ventilation (T2), and 15 minutes after inhaling air before leaving the room (T3). The content of IL-8 in arterial blood was measured by enzyme-linked immunosorbent assay (ELISA) at T0 and T2, and the expression of AQP1 protein in isolated lung tissue was measured by immunohistochemistry and Western blot. The incidence of postoperative pulmonary complications (atelectasis, pneumonia, and acute respiratory distress syndrome) was used as the index of lung injury. Results: There was no significant difference in the general condition before and during operation between the two groups. There was no significant difference in arterial blood IL-8 content between the two groups at the T0 time point, but the arterial blood IL-8 content at the T2 time point was significantly higher than that at the T0 time point, especially in group C. The results of immunohistochemistry and Western blot showed that the expression level of AQP1 protein in the isolated lung tissue of group D was significantly higher than that of group C (P < 0 05). At T3, the OI of group D was significantly higher than that of group C, and the A-aDO2 of group D was significantly lower than that of group C (P < 0.05). There was no significant difference in the incidence of postoperative PPCs between the two groups. Conclusion: Dexmedetomidine can reduce the level of plasma IL-8 and upregulate the expression of AQP1 in the lung tissue of patients undergoing thoracoscopic surgery under one-lung ventilation, but it has no significant effect on the incidence of postoperative PPCs. Dexmedetomidine can be safely used in thoracoscopic surgery and has a certain protective effect on lung injury. Copyright © 2020 Jun Meng et al.