Objective To investigate the protective efficacy of anisodamine against lung edema after ischemia-reperfusion in rabbits, and to explore the possible mechanism. Methods In vivo lung ischemia-reperfusion model of rabbit was developed. Twenty-four Chinese rabbits of either gender, aged 10-12 weeks, weighing 2200?2600 g, were divided into 3 groups randomly: anisodamine group, control group and sham group, with 8 rabbits in each group. In anisodamine group, the left pulmonary hilum was occluded for 1 hour and then released for 3 hours, and anisodamine (3 mg/kg) was given by intravenously injection before occlusion. In control group, only ischemia-reperfusion was performed. In sham group, left lung received no ischemia-reperfusion. Left lung tissue in each group was harvested for histopathological analysis, lung water content determination and myeloperoxidase (MPO) level detection. Also, 2% Evens blue (1.5 ml/kg) was injected into femoral venous to measure lung vascular permeability. Results After ischemia-reperfusion, the lung tissue water content, MPO level and Evens blue level in control group were (6.6±0.5) g/g dry tissue, (1.16±0.14) U/g protein and (173±16) μg/g wet tissue respectively, significantly higher than those in sham group [(4.3±0.4) g/g dry tissue, (0.53±0.09) U/g protein and (103±11) μg/g wet tissue, P＜0.05]. These indices in anisodamine group were (5.6±0.4) g/g dry tissue, (0.82±0.11) U/g protein and (124±18) μg/g wet tissue, obviously lower than those in control group (P＜0.05). Left lung displayed prominent edema, septal swelling, hemorrhage and neutrophil infiltration in control group, while which was significantly improved in anisodamine group. Conclusion Anisodamine can significantly prevent lung edema after ischemia-reperfusion in rabbits. The mechanism may be ascribed to inhibition of neutrophil infiltration and decrease in vascular permeability.