Human serum paraoxonase 1 (PON1) is a 43-kDa protein which catalyses the hydrolysis of organophosphate esters, aromatic carboxylic acid esters, and carbamates. PON1 is synthesized in the liver and is mainly associated with high-density lipoprotein (HDL). The enzyme decreases accumulation of the lipid peroxides in low-density lipoprotein (LDL) due to its ability to reduce hydroperoxides. PON1 activity was found to be decreased in diabetes mellitus. PON1 has a protective role against diabetes development, secondary to its unique antioxidant properties. The high concentrations of glucose in diabetic serum could account for PON1 dissociation from HDL. Furthermore, oxidative stress as a consequence of diabetes can increase the formation of lipid peroxides and reduce the activity of serum PON1. Polymorphisms in the promoter and coding regions of the paraoxonase gene are the main determinants of its expression and the enzymatic activity, but serum paraoxonase activity can be modulated by several environmental factors. Pathologic states such as renal disease, diabetes mellitus, cardiovascular disease, and liver cirrhosis are asociated with decreased paraoxonase activity, and various dietary and lifestyle factors have been reported to influence serum paraoxonase activity. The differences in paraoxonase activity among individuals are explained partly by genetic variation in th coding region of paraoxonase gene. The most famous variations are supstitution pf arginine for glutamine at position 192 (Q192R) and methionine for leucine at position 55 (M55L). The M55L polymorphisam is also a significant determinant of the serum concetration of paraoxonase.