Abstract: Objective To investigate the effect of receptor for advanced glycation end products (RAGE) on cell proliferation and tumor growth in nude mice with pancreatic cancer. Methods PANC-1 cells were transfected with shRNA RAGE -1,-2,-3 to down-regulate the expression of RAGE. Cholecystokinin octopeptide-8 (CCK-8), real-time PCR and Western blot were performed to test the impact of shRNA RAGE on the expressions of mRNAs and proteins of RAGE, matrix metalloproteinase-2 (MMP-2), MMP-9, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and vascular endothelial growth factor (VEGF). Tumor growth and microvessel density in the nude mice implanted with shRNA RAGE transfected PANC-1 cells were observed using immunohistochemistry. Results The shRNA RAGE -1,-2,-3 transfected cells had lower absorbance values than the controls 24 h after transfection, and the absorbance value reached the lowest at 48 h. The specific shRNA sequences significantly inhibited the expressions of mRNA and protein of RAGE. The mice implanted with shRNA RAGE -2 had lower tumor volume and microvessel density than shRNA RAGE -1,-3. The expressions of mRNAs and proteins of RAGE, MMP-2, NF-κB, MMP-9 and VEGF were lower in the cells transfected with shRNA RAGE -2 compared with shRNA RAGE -1,-3. Conclusion RAGE is involved in the progression of pancreatic cancerin vitro and in vivo . The RAGE expression could influence the process of tumor angiogenesis.