Abstract: Objective To investigate the effect of melatonin on lung ischemia / reperfusion (I /R) injury in diabetes mellitus ( DM) rats and its underlying molecular mechanism. Methods Rats were randomly divided into Control + Sham operation group (Control + Sham group), diabetes +Sham operation group ( DM + Sham group), Control + ischemia-reperfusion group ( Control + IRgroup), diabetes + ischemia-reperfusion group (DM + IR group), diabetes + ischemia-reperfusion +melatonin group (DM + IR + MT group), 8 rats in each group. The wet / dry weight ratio ( W / D)was measured in each group. Hematoxylin-eosin (HE) staining was used to detect the pathologicalchanges of lung tissues in each group. The activity of oxidative stress factor glutathione peroxidase(GSH-PX), superoxide dismutase ( SOD) and malondialdehyde ( MDA), and the level of totalantioxidant capacity (T-AOC) were detected in the lung tissues of rats in each group. The levels ofinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The expression levels of p-JAK2 and p-STAT3 were detected by Western blotting. Results Compared with those in the Control + Sham group, the ratio of W/ D wasincreased, the alveolar septum and space edema, the interstitial thickening, and the alveolar hemorrhage and leukocyte infiltration were found, the lung injury score was higher, the activities of GSH-Px, SOD and T-AOC were decreased, and the level of MDA was increased, the levels of IL- 1β, IL-6 and TNF-a were increased, and the expression levels of p-JAK2 and p-STAT3 were increased in the Control + IR group (P< 0. 05). The above indexes were further increased in the DM+ sham group and the DM + IR group, and the difference was more significant in the DM + IR group. Compared with those in the DM + IR group, the ratio of W/ D was significantly decreased, the injuries in the lung tissue were significantly reduced, the lung injury score was decreased, the activities of GSH-Px, SOD and T-AOC were increased, and the level of MDA was decreased, the levels of IL-1β, IL-6 and TNF-α were decreased, and the expression levels of p-JAK2 and pSTAT3 were decreased in the DM + IR + ME group (P< 0. 05). Conclusion Melatonin attenuatedlung I / R injury the diabetic rats by reducing oxidative stress and inflammation, and its mechanism could be related to the JAK2 / STAT3 signaling pathway.

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