Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps release. However, its role in cardiac surgery and the mechanisms behind neutrophil extracellular traps suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on neutrophil extracellular traps inhibition as a novel therapeutic strategy. Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for seven days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 hours. Immunofluorescence detected neutrophil extracellular traps, and Hematoxylin and Eosin staining assessed inflammatory cell. We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of neutrophil extracellular traps in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4(PAD-4) was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of neutrophil extracellular traps by inhibiting PAD-4. NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting neutrophil extracellular traps formation, with PAD-4 inhibition being one of its mechanisms.