Objective To explore the expression of the receptor for advanced glycosylation end products(RAGE) and its intracellular signaling molecules DIAPH1 in lung adenocarcinoma A549 cells and the effect of RAGE ligands on cell migration and apoptosis. Methods The expressions of RAGE and DIAPH1 in lung adenocarcinoma A549 cells and human bronchial epithelial cells BEAS-2B were tested by qRT-PCR and Western blot. A549 cells was treated with 10,100 μg /ml RAGE ligands CML-AGE and 1,10,100 μg /ml S100B,and wound healing test was used to identify the effect of migration ability. A549 cells was treated with 25,50,100 μg /ml RAGE ligands CMLAGE, the gene expression of BCL-2 and BAX were tested by using qRT-PCR. Results The results of qRT-PCR and Western blot showed,compared with human bronchial epithelium cells BEAS-2B,the expression of RAGE and DIAPH1 were both significantly down-regulated in lung adenocarcinoma A549 cells (P < 0. 001). After treated with 10,100 μg /ml RAGE ligands CML-AGE and 1,10,100 μg /ml S100B ,both groups showed the ligands inhibit lung adenocarcinoma A549 cells migration in concentration-depend manners (P < 0. 01). After treated with 25, 50,100 μg /ml RAGE ligands CML-AGE,the expression of anti-apoptotic gene BCL-2 was down-regulated and proapoptotic gene BAX was upregulated in the experimental group in concentration-depend manners(P < 0. 05),the difference was significant. Conclusion The expression levels of RAGE and DIAPH1 in lung adenocarcinoma A549 cells are both significantly lower than human bronchial epithelium cells BEAS-2B. RAGE ligands can inhibit cells migration and promote cell apoptosis in lung adenocarcinoma A549 cells and may provide a new target for the therapy of lung adenocarcinoma cells.