Objective To observe the effects of melatonin on lung injury and NDRG2 ( N-myc downstream-regulated gene 2) expression after intestinal ischemia-reperfusion ( I/R) .Methods 40 healthy SD rats were randomly assigned to a sham group, an I/R group, a high-dose melatonin group ( 10 mg/kg) , and a low-dose melatonin group ( l mg/kg) . The model of lung injury was established by superior mesenteric artery clamping/unclamping. 30 minutes before clamping, melatonin was administered intraperitoneally to the rats in two melatonin groups, and normal saline in same volume was administered to the rats in the I/R group and the shamgroup. Then superior mesenteric arteries of the rats in the I/R group and two melatonin groups were clamped for 60 minutes. 45 minutes after unclamping, right lung tissues were sampled for pathological examination and wet/dry ( W/D) ratio measurement. The rats in the sham group underwent sham operation without clamping. The expression of NDRG2 protein in the lung tissue was detected by immunohistochemistry and Western-blot. Results Compared with the sham group, hemorrhage and inflammation of lung tissues were observed. The W/D was obviously increased and the NDRG2 expression was significantly decreased in the I/R group. Compared with the I/R group, mild hemorrhage and inflammation changes of lung tissues were observed and the W/D was decreased while the NDRG2 protein expression was increased significantly in two melatonin groups. There was no significant difference between two melatonin groups. Conclusion Melatonin may relieve lung injury after intestinal ischemia-reperfusion through up-regulating NDRG2 expression.