Abstract: Paraoxonase 1 is an esterase that associates with other enzymes to detoxify organophosphate pesticides. The expression and activity of paraoxonase is due to polymorphisms of the paraoxonase gene. Thus, the present study aimed to determine the activity of paraoxonase and paraoxonase genotypes along with their relationships, the risks and medical conditions in Iranian workers that were occupationally exposed to organophosphates. Workers (n = 80) exposed to organophosphates and controls (n = 160) that were not exposed to Organophosphates gave a blood sample in order to have two polymorphisms of paraoxonase, paraoxonase activity buthyrylcholinesterase activity and their interactions investigated. The results showed that the exposed group had significantly (p<0.05) less paraoxonase activity than the controls (90.04±4.632 and 149.8±5.236 nmol min-1 mL-1, respectively). The Q/Q, Q/R and R/R genotypes (highest to lowest rates, respectively) significantly hydrolyzed paraoxon (i.e., paraoxonase activity) in both groups (p<0.001). Paraoxonase activity was higher in subjects with L/L genotypes and was the lowest in individuals with M/M genotypes in the exposed and control groups. The results indicate that individuals with paraoxonase R/R and M/M genotypes may be more susceptible toward organophosphate toxicity. Enzymatic activities were widely varied and it appears that the differences in genotypes can cause the changes in this activity. Thus, these different genotypes may be important biomarkers in protecting individuals and identifying individual risk factors in workers exposed to organophosphates.