Abstract.Objective.  To investigate the paraoxonase‐2 (PON2)‐C/S310 polymorphism and its relationship to the presence of diabetic complications and glycaemic control.Design.  Case–control study.Setting.  One study centre at University hospital.Materials and methods.  The subjects were people with type 2 diabetes (n = 252), type 1 diabetes (n = 152) and healthy controls (n = 282). The PON2‐C/S310 polymorphism was measured by restriction fragment length polymorphism analysis. Lipids and lipoproteins were measured by standard clinical chemistry methods. Diabetes and diabetic complications were defined by World Health Organization criteria.Results.  There was an over‐representation of the C/C310 genotype in those with diabetes and microvascular complications (type 2 diabetes P = 0.043, type 1 diabetes P = 0.052, both populations combined P = 0.014). The PON2‐C/S310 polymorphism was also associated with glycaemic control. C310/C310 homozygotes had the highest HbA1c concentration (P = 0.020 type 2 diabetes, P = 0.065 type 1 diabetes, P = 0.035 both populations combined). There was no association between the PON2‐310 polymorphism and lipid and lipoprotein concentrations.Conclusions.  PON2 could be directly involved in protecting critical enzymes or organelles against oxidative damage; PON2 may thus predispose to the development of microvascular complications.