【Objective】To study the association of CAV1/CAV2 gene polymorphisms with type 2 diabetes in Chinese Han population.【Methods】14 single nucleotide polymorphisms（SNPs）of CAV1/CAV2 gene were genotyped in 272 pa? tients with type 2 diabetes mellitus（T2DM group）and 287 subjects with normal glucose tolerance（control group）by ma? trix-assisted laser desorption ionization-time of flight-mass spectrometry（MALDI-TOF-MS）. Waist circumference，body mass index，plasma glucose，serum insulin and lipid profiles were measured.Homeostatic model assessment of insulin resis? tance（HOMA-IR）and β-cell function（HOMA-β）were calculated.【Results】The minor allele frequency（MAF）distri?butions of CAV1 rs926198，CAV2 rs2270188，and rs1052990 were significantly different between T2DM group and con? trol group（P=0.008，0.021，and 0.045，respectively）. After adjusting for age，gender，and BMI，logistic regression analysis showed that minor allele carriers（CC/CT genotype）of CAV1 rs926198 displayed a particularly increased risk of developing T2DM compared to major allele homozygotes（TT genotype）（OR=2.240，95%CI=1.415-3.544，P=0.001）. GG/GA genotype carriers of CAV1 rs3807986 had lower odds for T2DM than that of AA genotype（OR=0.640，95%CI= 0.449-0.913，P=0.014）. Compared with TT genotype，GG/GT genotype of CAV2 rs2270188 was a protective factor for T2DM（OR=0.616，95%CI=0.432-0.878，P=0.007）. Significant genotype association with T2DM was also identified in CAV2 rs1052990（GG/GT versus TT genotype：OR=0.658，95%CI=0.453-0.956，P=0.028）. Multiple linear regression showed that minor allele C of SNP rs926198 was associated with an increased level of HOMA-IR（beta=1.010，P<0.001） and minor allele G of SNP rs2270188 was associated with a decreased level of HOMA-IR（beta=-0.379，P=0.023）. No significant association was identified between any SNP and HOMA-β. Allele G of CAV1 rs3807986 and CAV2 rs2270188 were also associated with a decreased level of LDL-C（P=0.033 and 0.030，respectively）.【Conclusion】CAV1/CAV2 locus might be the candidate genes for conferring susceptibility to T2DM in the Chinese Han population.SNP rs926198， rs3807986，rs2270188，and rs1052990 in CAV1/CAV2 locus were associated with T2DM risk perhaps through insulin resistance pathway.