Aim To investigate the association between paraoxonase 2 gene 311 Cys/Ser polymorphism and macrovascular disease in type 2 diabetes mellitus patients. Methods A case-control study of 272 subjects(including randomly selected 183 type 2 diabetes mellitus patients with or without macrovascular disease and 89 healthy controls) was performed.Genomic DNA was extracted from the subjects'peripheral blood leukocytes.The paraoxonase 2 gene 311 Cys/Ser polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with Ddel Ⅰ digestion. Results Paraoxonase 2 gene 311 Cys/Ser polymorphism was detected in population of Qingdao.The genetype distribution(CC, CS and SS) of paraoxonase 2 gene 311 Cys/Ser polymorphism showed significant differences between type 2 diabetes mellitus complicated with macrovascular disease group and the other two groups(type 2 diabetes mellitus group & healthy group),the former had significantly higher S allele frequency(p<0.05 or p<0.01).The ratio of diabetic macrovascular disease,if S allele existed,increased(2.932) times.Levels of serum lipids in different genotypes of paraoxonase 2 gene 311 Cys/Ser in cases showed no evident differences. Conclusions The paraoxonase 2 gene 311 Cys/Ser polymorphism is associated with type 2 diabetes mellitus complicated with macrovascular disease in Qingdao's population.S allele may be a risk factor for type 2 diabetes mellitus complicated with macrovascular disease.