Variants of calpain-10 gene (CAPN 10) have recently been reported to be associated with type 2 diabetes (T2DM). Haplotype combination 112/121 defined by three single nucleotide polymorphisms (SNPs) (UCSNP-43, -19 and -63) of CAPN 10 conferred the highest risk for T2DM in Mexican-Americans. In this study, we aim to examine whether these genetic variants contribute to the susceptibility for T2DM in a Chinese population. The frequencies of these three SNPs were determined in 168 patients with T2DM and 104 controls. Distribution of alleles, genotypes and haplotypes at three loci were not significantly different between the two groups. No difference was observed in the 112/121 haplotype combination distribution. However, haplotype combination 112/221 was more prevalent in the control group than in T2DM group (16.35% versus 7.14%, p = 0.025). Control subjects with haplotype combination 112/121 had higher serum cholesterol level than others without haplotype combination 112/121 (5.7 +/- 1.4 versus 5.2 +/- 0.7, p = 0.011). Our results suggest that haplotype combination 112/221 associated with reduced risk for T2DM and haplotype combination 112/121 might be a risk factor for increased serum cholesterol in Chinese population.