It was demonstrated in the present study that the KOR agonist U50448H improved lung function, mitigated lung injury, decreased ROS and MMP-9 expression in lung tissues, augmented macrophage polarization from M1 to M2, and reduced NLRP3 inflammasomes in CPB rats, proposing U50448H as a promising drug for the treatment of ALI secondary to CPB. Here, NLRP3 is linked to acute respiratory distress syndrome.