Purpose Higher soluble receptor for advanced glycation end products (sRAGE) levels are considered to be associated with severe emphysema. However, the relationship between sRAGE, emphysema and the polymorphism of rs2070600 in advanced glycation end-product specific receptor (AGER) gene remains uncertain. To investgate the relationship, we analyzed association of sRAGE and emphysema according to the genotypes of rs2070600. Methods We genotyped rs2070600 polymorphism in participants. Plasma concentration of sRAGE was measured using enzyme-linked immunosorbent assay. Emphysema was quantified based on chest computer tomography of each participant. We compared level of sRAGE according to presence and severity of emphysema in each genotype. Moreover, we used multiple logistic regression and linear regression model for control covariates. Results In total, 436 participants were included in this study. Among them, 280 (64.2%) were chronic obstructive pulmonary disease (COPD) patients and 166 (38.1%) had emphysema. The level of sRAGE was significantly high in participants without emphysema compared to those with emphysema in COPD patients with CC genotype (P<0.0001). Also, the level of sRAGE was negatively correlated with emphysema severity in COPD patients with CC genotype (r=-0.295, P<0.0001). Multiple regression analysis revealed that sRAGE was independent protective factor for presence of emphysema (odds ratio 0.257 CI, 0.120-0.551) and severity of emphysema (β=-3.289, P<0.001) in CC genotyped participants after adjusting age, sex, smoking status, body mass index and presence of COPD. Conclusion Plasma sRAGE might be a biomarker with protective effect on emphysema in certain subgroup, COPD patients with CC genotype of rs2070600 on AGER gene. This is important in determining the target group for future treatment for emphysema.