Abstract: Objective To explore the effects of transfection of endogeny polypeptide elafin on mucin (MUC)5AC overexpression induced by lipopolysaccharide. Methods Eukaryotic expression vector pEGFP-N1-Elafin was constructed and transfected into HBE16 Cells. Cells were then stimulated by lipopolysaccharide (LPS). Elafin was detected by immunofluorescence and observed by Confocal Laser Scanning Microscopy (CLSM), the protein level inhibitor of NF-κB (IκB)α was detected by western blot, the transcription activity of nuclear factor κB (NF-κB) was detected by luciferase reporter gene detection system, MUC5AC protein level was assessed by ELISA, the levels of Elafin mRNA and MUC5AC mRNA were detected by RT-PCR, respectively. Results The levels of Elafin protein and mRNA were obviously increased after transfection of recombinant Elafin into HBE16 cells, compared with LPS group or control group. There was an obvious increase of MUC5AC protein production and mRNA expression, with elevation of NF-κB activity, all significantly higher than control group, IκBα protein production was significantly lower than control group. Transfected recombinant elafin reduced MUC5AC protein and mRNA level, inhibited NF-κB activity, and increased IκBα protein production, compared with single LPS-stimulated group. Conclusion Transfection of endogeny polypeptide Elafin may down-regulate MUC5AC overexpression induced by LPS, and this is through the inhibition by Elafin of NF-κB activiation via effects on IκB pathway.