Aim To analyze if the mutation of estrogen receptor (ER) gene has any relationship with macroangiopathy (MA) in men and postmenopausal women with type 2 diabetes (T2DM). Methods ER genotyping was performed by using PCR-RFLP method in 118 T2DM patients with and without MA and 32 normal controls (NC), which were men and postmenopausal women. The serum E₂ and lipid levels were also determined. Results ER allelic frequencies of X, x and P,p alleles were 0.208, 0.792; 0.432, 0.568 and 0.266, 0.734; 0.50, 0.50 in T2DM group and control group respectively. There was no significant difference in frequencies of allele and genotype in XbaI polymorphism or XbaI with PvuⅡ polymorphisms together between these two groups. The Pp and PP genotypes were significantly more frequent in subjects with IMT>1.0 mm than in those without MA (86.7% vs 58.3%, p<0.05). In subjects of T2DM, serum TC and LDLC levels were significantly higher in subjects with the Xx genotype compared with those with the wild genotypes [(5.33±1.06) mmol/L vs (4.81±0.99) mmol/L p<0.01; (3.43±0.72) mmol/L vs (3.08±0.8) mmol/L p<0.05 respectively]. The serum E₂ level was significantly higher in CVD group than group without MA [(34.59±16.8) ng/L vs (26.46±11.98) ng/L, p<0.05]. The mutation genotypes of XbaI and PvuⅡ were significantly and positively correlated with TC and LDLC levels respectively (r=0.2671 P=0.005 and r=0.2483 P=0.010; r=0.2301 P=0.017 and r=0.2172 P=0.024 respectively). The PvuⅡ polymorphism was the independent risk factor for MA (Or=2.996, 95%CI 1.023～8.767, P=0.041). Conclusion The mutation of ER gene in men and postmenopausal women with T2DM might result in the change of serum lipid levels. The higher E₂ level might have the relationship with the endpoint of CVD. XbaI polymorphism is not related with MA, but PvuⅡ polymorphism might be a risk factor for MA in men and postmenopausal women with T2DM.