The main causes of lung injury after cardiopulmonary bypass (CPB) are systemic inflammatory response syndrome (SIRS) and pulmonary ischaemia‐reperfusion injury (IR‐I). SIRS and IR‐I are often initiated by a systemic inflammatory response. The present study investigated whether the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors (FPRs) inhibit inflammatory cytokines and reduce lung injury after CPB. Male rats were randomized to the following five groups (n = 6, each): sham, exposed to pulmonary ischaemic‐reperfusion (IR‐I), IR‐I plus Ac2‐26, IR‐I plus the FPR antagonist, BoC2 (N‐tert‐butyloxycarbonyl‐Phe‐Leu‐Phe‐Leu‐Phe) and IR‐I plus Ac2‐26 and BoC2. Treatment with Ac2‐26 improved the oxygenation index, an effect blocked by BoC2. Histopathological analysis of the lung tissue revealed that the degree of lung injury was significantly less (P < 0.05) in the Ac2‐26‐treated rats compared to the other experimental groups exposed to IR‐I. Ac2‐26 treatment reduced the levels of the inflammatory cytokines TNF‐α, IL‐1β, ICAM‐1 and NF‐κB‐p65 (P < 0.05) compared to the vehicle‐treated group exposed to IR‐I. In conclusion, the annexin A1 (ANX‐A1) peptidomimetic Ac2‐26 by binding to formyl peptide receptors inhibit inflammatory cytokines and reduce ischaemic‐reperfusion lung injury after cardiopulmonary bypass.