The apolipoprotein gene cluster (APOA1/C3/A4/A5) was recently associated with triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) in non-diabetic population. Little is known whether the variations in these genes affect lipid homeostasis in patients with type 2 diabetes. We examined the associations of 10 polymorphisms at APOA1/C3/A4/A5 gene cluster with blood lipids among 902 diabetic women. A linkage disequilibrium (LD) breakdown was observed between APOA5 and other genes. APOA5 S19W was associated with significantly higher fasting TG levels (P=0.001). Two common haplotypes encompassing four APOA5 polymorphisms (SNP1, SNP2, S19W, and SNP3) were associated with 35.6 mg/dL (haplotype 2212, APOA5*2, P=0.016) and 57.8 mg/dL (haplotype 1121, APOA5*3, P=0.0002) higher fasting TG levels compared with the most common (haplotype 1111, APOA5*1), respectively. Adjustment for age, BMI, and other covariates did not appreciably change such associations. In addition, APOC3 promoter polymorphism -455T/C showed significant associations with fasting TG levels (P=0.006), whereas APOA4 +347T/A showed significant associations with lower levels of HDL-C (P=0.017). Our results indicate that the variability in APOA1/C3/A4/A5 gene cluster may affect TG and HDL levels in women with type 2 diabetes.