Abstract: Objective To investigate the secretory mechanism of interleukin (IL)-6 when bronchial epithelial cells were co-cultured with neutrophils. Methods Neutrophils were isolated by immune-magnetic beads positive selection method and a system of human bronchial epithelial cells co-cultured with human neutrophils was constructed. The level of IL-6 was detected by the Cobas e411. Results The level of IL-6 (3 691±482.3) pg/ml in the supernatant was signifcantly higher than the cells cultured singlyBEAS-2B (313.4±34.7) pg/ml; NEU (219.1±11.3) pg/ml, (P< 0.001). Western blotting suggested that NF-κB and p38-MAPK in BEAS-2B could be activated when BEAS-2B was co-cultured with neutrophils. The release of IL-6 could be inhibited effectively with MG-132 (the proteasome inhibitor of NF-κB)(1 075.3±83.9) pg/ml vs (3 691±482.3) pg/ml, P< 0.01. SB203580, the proteasome inhibitor of p38-MAPK, could also inhibit the release of IL-6(1 532.8±176.1) pg/ml vs (3 691±482.3) pg/ml, P< 0.01. However, the MG-132 performed better than SB203580 in inhibiting the release of IL-6(1 075.3±83.9) pg/ml vs (1 532.8±176.1) pg/ml, P< 0.01. The release of IL-6 decreased further when treated with the two inhibitors(353.1±33.5) pg/ml vs (1 075.3±83.9) pg/ml) P< 0.01; (353.1±33.5) pg/ml vs (1 532.8±176.1) pg/ml, P< 0.01. Conclusion The signal transduction pathway of NF-κB and p38MAPK in BEAS-2B can be activated, which can regulate the release of IL-6, when BEAS-2B are co-cultured with neutrophils.