Abstract： Objective To test the role of paraoxonase (PON) 2 gene in the pathogenesis of type 2 diabetes mellitus in Chinese population. Methods The PON2 gene G/A148 polymorphism was detected by polymerase chain reaction (PCR) and appropriate restriction enzyme (PCR RFLP) in 132 couples of type 2 diabetes spouse based controls. Results The genotype frequency and allele frequency were not different between the case and the control group. Compared with non obesity subjects without G allele, the obesity subjects without G allele and the obesity subjects with G allele had an OR for type 2 diabetes of 2.04, 3.18, respectively. In control group, the levels of total and low density lipoprotein cholesterol and apolipoprotein B (ApoB) were higher in the GA/GG genotype than that in the AA genotype and the OR of G allele for hyperlipidemia was 2.48, P =0.05. Conclusion There were synergistic effects between the PON2 gene G allele and obesity on type 2 diabetes mellitus. PON2 gene G/A148 polymorphism was significantly associated with total cholesterol level in non diabetic Chinese population.