Extracellular high-mobility group box-1 (HMGB-1) has been implicated in the inflammation response leading to the precancerous lesions of non-small cell lung cancer (NSCLC). However, the role of HMGB-1 in the inflammation response in normal human bronchial epithelial (NHBE) cells and its underlying mechanisms were still not fully understood. In this study, the inflammation response in NHBE cells was stimulated by 2.5, 5, and 10 μg/ml HMGB-1. However, the receptor for advanced glycation end products (RAGE) blocker RAGE-Ab (5 μg/ml) or 10 μM c-Jun N-terminal kinases (JNK) inhibitor SP600125 could inhibit HMGB1-induced the release of inflammation cytokines including TNF-α, IL-8, IL-10, and MCP-1 in a dose-dependent manner. Furthermore, HMGB1-induced RAGE protein expression, JNK and NF-κB activation were attenuated by the pretreatment with RAGE-Ab or JNK inhibitor SP600125 in Western blot analysis. Our data indicated that HMGB-1 induced inflammation response in NHBE cells through activating RAGE/JNK/NF-κB pathway. HMGB-1 could act as a therapeutic target for inflammation leading NHBE cells to the precancerous lesions of NSCLC.