Background: Recent studies have proposed that the serine protease inhibitor E2 (SERPINE2) was a novel susceptibility gene for chronic obstructive pulmonary disease (COPD) in Caucasians. However, this issue still remained controversial. Additional evidences from populations with different environments and/or genetic backgrounds, such as East Asian, would be helpful to elucidate the issue. Methods: In this study, five proposed causal SNPs in SERPINE2 were genotyped in 327 COPD patients and 349 controls, all of which belonged to the Han population sampled from Southwest China. The frequency of each SNP was compared both individually and in combination between patients and controls. The potential relationship between these SNPs and severity of COPD was also investigated. Results: Three SNPs (rs3795877, rs6747096, and rs3795879) showed complete linkage disequilibrium (r(2) = 1), and the minor allele frequencies were 13.0% and 12.9% in case and control cohorts, respectively, with no significant difference observed (P = 0.96). We also failed to observe any significant correlation between these SNPs and COPD severity (P = 0.67). The other two SNPs (rs7579646 and rs840088) also presented a similar pattern. Moreover, four major haplotypes were observed in our sample but none showed a significant difference between case and control groups (P > 0.1). Conclusion: Our results failed to obtain the evidence that these SNPs in SERPINE2 contributed to the COPD susceptibility in the Han Chinese population.