Objective To study the effect of dexmedetomidine (DEX) combined with ulinastatin (UTI) on inflammatory response induced by oesophagectomy with one-lung ventilation (OLV). Methods Seventy-two patients with esophageal cancer (ASA Ⅰ～Ⅱ) scheduled for oesophagectomy via left thoracotomy were randomly divided into four groups (n=18 each): control group (group C), DEX group (group D), ULI group (group U) and DEX combined with UTI group (group D+U). Anesthesia induction and perioperative management followed the same protocols in all groups. In group D, 10min after tracheal intubation, DEX 1μg/kg was infused for 10min, followed by continuous infusion of DEX at the rate of 0.5μg•kg-1•h-1. In group U, ULI 10 000 U /kg was intravenously infused 10min after tracheal intubation for 10 min. In group D+U, the infusion protocol of DEX and ULI was the same as in group D and group U, respectively. Normal saline with equal volume were administrated in group C. At four time points: before operation (T0), 1h (T1) and 2h (T2) after one-lung ventilation (OLV), and 2h (T3) after operation, blood samples were collected for determining PaO2 and PaCO2 and the serum levels of high mobility group box-1 protein (HMGB1)、tumor necrosis factor (TNF)-α、interlukin (IL)-6、IL-8 and IL-10 were detected and compared. Results Compared with group C, PaO2 were higher in D and U groups, which were lower than those of group D+U (P＜0.05). Compared with T0, HMGB1, TNF-α, IL-6, IL-8 and IL-10 levels increased significantly at T1, T2 and T3 in all groups (P＜0.05). Compared with group C, the serum levels of HMGB1 were lower at T1 [(3.77±0.32) vs (4.46±0.28), (3.80±0.22) vs (4.46±0.28) , (3.12±0.02) vs (4.46±0.28)]、T2 [(4.38±0.16) vs (5.89±0.36), (4.33±0.27) vs (5.89±0.36), (3.94±0.24) vs (5.89±0.36)]、T3 [(7.32±0.43) vs (9.84±0.82), (7.71±0.39) vs (9.84±0.82) , (5.88±0.36) vs (9.84±0.82)] in D, U and D+U groups (P＜0.05), but the levels of IL-10 were higher [(38.44±5.80) vs (33.29±6.23), (39.30±5.46) vs (33.29±6.23) , (44.07±3.72) vs (33.29±6.23)], [(62.29±10.02) vs (44.87±11.24), (63.02±2.90) vs (44.87±11.24) , (70.89±5.73) vs (44.87±11.24)], [(89.10±10.27) vs (63.27±9.48), (88.36±6.36) vs (63.27±9.48) , (97.89±10.20) vs (63.27±9.48)] (P＜0.05). The serum levels of HMGB1 were lower at T1, T2 and T3 in group D+U than D and U groups (P＜0.05). The serum levels of IL-10 were higher at T1, T2 and T3 in group D+U than group D and group U (P＜0.05). The serum levels of TNF-α, IL-6 and IL-8 were lower at T1, T2 and T3 in D, U and D+U groups than group C and were lower in group D+U than group D and group U (P＜0.05). Conclusions DEX combined with UTI could inhibit inflammatory response induced by oesophagectomy and may be related to alleviation of OLV-induced lung injury.