To evaluate the efficacy of taurolidine instillation on postoperative air leak by clinical study and to investigate the mechanism of action by animal experiments.Outcomes of taurolidine instillation in patients with postoperative air leak were retrospectively reviewed. 100 ml of 1% taurolidine solution was instilled through a chest tube in patients with postoperative air leak lasting 4days or more. Success was defined as cessation of air leak within 24 hours with full expansion of lung on chest radiograph and subsequent removal of chest tube within another 24 hours. The effect of taurolidine instillation was estimated by development of adhesion and thickening of the visceral pleura in rabbits. The study group was compared with a control group and a talc poudrage group.Out of 75 patients, the success rate was 66.7%. Out of 96 total attempts, taurolidine instillation was successful in 55%. In animal experiments, pleural adhesion was minimal in the taurolidine and control groups, whereas the talc group showed more adhesions. The taurolidine group showed a moderate visceral pleural thickening. The talc group showed severe visceral pleural thickening, whereas the control group showed mild thickening.Taurolidine is an effective alternative agent for the management of air leak. A chemical sclerosing effect is suggested as the mechanism of air leak cessation.