Objective:To observe the effect of annexin A1 peptidomimetic Ac2-26 on lung injury in rats with cardiopulmonary bypass, and analysis its anti-inflammatory mechanism.Methods:Eighteen male SD rats were divided into 3 groups(n=6) according to the random number table: sham operation group(S group), ischemia reperfusion group(IR group), Ac2-26 group(A group). The sham operation group received femoral arteriovenous puncture and catheterization, only the left lung was opened and the cardiopulmonary bypass tube was not connected. The other two groups were established with cardiopulmonary bypass left lung ischemia-reperfusion injury model. The IR group was given the same volume 10 minutes before cardiopulmonary bypass with the normal saline solution. Group A was injected with Ac2-26(1 mg/kg) through the tail vein 10 minutes before cardiopulmonary bypass. The arterial blood of the three groups of rats was taken for blood gas analysis before CPB(T1), immediately after opening the left lung hilum(T2), and at the end of the experiment(T3) to calculate OI and RI. At T1 and T3, the femoral vein blood was taken to measure the number of PMN. At T3, pulmonary artery blood was taken to measure the number of PMN and VCAM-1 content, left lung tissue was taken to measure NE and MPO content by ELISA, lung tissue neutrophil apoptosis was measured by Tunel method, and lung tissue ICAM-1 and AnxA1 protein expression was measured by Western-Blot.Results:At T3, compared with group S, the number of PMN in peripheral blood and pulmonary artery blood and the content of pulmonary artery VCAM-1 in IR group were significantly higher, the content of MPO and NE in lung tissue increased, the lung tissue pathological damage score increased, OI decreased and RI increased, all P<0.05. Compared with IR group, the lung tissue pathological damage score of rats in group A was significantly reduced, the number of PMN in peripheral blood and pulmonary artery blood and the content of VCAM-1 in pulmonary artery blood were significantly reduced, the expression of AnxA1 and ICAM-1 in the lung tissue of rats decreased; the content of MPO and NE in lung tissue decreased, and the apoptosis rate of PMN increased, all P<0.05. Conclusion:Ac2-26 annexin A1 peptidomimetics can inhibit the aggregation of neutrophils in the lung, weaken the adhesion of neutrophils to the pulmonary vascular endothelium, promote the apoptosis of neutrophils in the lungs, and reduce the content of NE and MPO. It has a protective effect on lung injury after cardiopulmonary bypass in rats.