Objective To investigate the association between low-density lipoprotein receptor-related protein 5(LRP5) variants(rs12363572 and rs4930588) and type 2 diabetes mellitus(T2DM) in Han Chinese. Methods A total of 1842 T2 DM cases(507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms(SNPs). Odds ratios(ORs) and 95% confidence intervals(95% CIs) were calculated to describe the strength of the association by logistic regression. Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2 DM, even after adjusting for relevant covariates. When stratified by body mass index(BMI), the two SNPs were also not associated with T2 DM. Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM(OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI(P<0.001) and rs4930588 was associated with triglyceride levels(P=0.043) in 507 newly diagnosed T2 DM cases but not in healthy controls. Conclusion No LRP5 variant was found to be associated with T2 DM in Han Chinese, but haplotype TT was found to be associated with T2 DM. Objective To investigate the association between low-density lipoprotein receptor-related protein 5 (LRP5) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. Methods A total of 1842 T2 DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs Results In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2 DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P <0 .001) and rs4930588 was associated with triglyceride levels (P = 0.043) in 507 newly diagnosed T2 DM cases but not in healthy controls. Conclusion No LRP5 variant was found associated with T2 DM in Han Chinese, but haplotype TT was found to be associated with T2 DM.