Objective To investigate the effect of activation of NF-κB signaling pathway on pathogenesis of lung in diabetes mellitus(DM) rat. Methods The experimental type 2 diabetic rats were built by injecting streptozotocin (STZ) and feeding with high fat and glucose food. At the 12nd and 24th week, we observed the alteration of morphology in the lung of rats in the control group(20 rats) ,the DM group(30 rats)using spectroscopic analysis. The collagen accumulation of lung was observed by masson trihrome staining, and alteration of NF-κB P65, IκBα, and PKC in lung was observed by immunohistochemistry. Results The tissue structure of lung in the DM rats distributed deranged in the light microscope, alveolar wall were thicken, extracellular matrixes increased and pulmonary fibrosis appeared. With the development of pathogenic condition, the expression increased obviously. The staining optical density value of NF-κB P65 in tissue of lung in the 12 w and 24 w DM group were 0. 20 ± 0. 01 and 0. 35 ± 0. 06 respectively, which was significantly higher than those of the control group at the corresponding time point ( 0. 12 ± 0. 02 and 0. 17 ± 0. 03, respectively, Ps ＜ 0. 0l ). The staining optical density value of IκB in tissue of lung in the 12 w and 24 w DM group were 0. 29 ±0. 02 and 0. 36 ± 0. 03, respectively, which were significantly higher than those of the control at the corresponding time point (0. 08 ± 0. 02 and 0. 22 ± 0. 08, respectively, Ps ＜ 0. 01 ). Conclusion The signaling pathway of NF-κB/IκB participate in the occurrence and development in the pathogenesis of lung in DM, and may be one of the mechanisms of lung injury.