Background and objectives: Organophosphorus insecticides result in a huge number of intoxications because of the widespread use and the easy accessibility. Metabolism of organophosphorus compounds depends on a diversity of enzymes; the most important of which are paraoxonase and cytochrome P450. The present study aims to identify a possible association between the paraoxonase enzyme activity and the susceptibility for organophosphorus poisoning in both acute and chronic forms. Genetic polymorphism of PON1 192 and CYP-2D6 genes are studied to investigate individual susceptibility to organophosphorus poisoning.Methods: 99 adult subjects of both sexes were recruited for the study. They were divided into three groups; negative controls, acute OP intoxicated patients and chronic OP exposed subjects. They were subjected to sociodemographic, clinical and lab evaluation. Pseudocholinesterase level, paraoxonase activity level, and SNPs polymorphism of PON1 Q192R and CYP2D6 were determined and data were statistically analyzed.Results: The mean age of the patients was about 34 years. Acute intoxication was mostly due to suicidal attempts, the highest incidence was among housewives and most cases were intoxicated by ingestion. PON1 activity and cholinesterase levels were significantly lower in acute intoxicated patients while PON1 activity showed upregulation in chronic cases. There is an increase in PON1 192 mutant allele with increase in duration of exposure in chronic cases. Polymorphisms of both studied genes have insignificant influence on PON1 activity as well as choline esterase level.