Background/Aims: It is now known beyond doubt that viral hepatitis (caused by B or C virus) along with bilharzial infestation (mostly S. mansoni) are the most important factors responsible for the vast majority of morbidity and mortality in Egypt. Based upon the concept that oxidative stress plays a key role in the development and pathogenesis of chronic liver diseases, many of the factors known to have antioxidant properties are to be investigated for purpose of evaluating their role in the defense mechanisms against all oxidant brunts associated with liver diseases. Serum MDA was assayed as a famous marker of oxidative stress, while PON1 enzyme activities were investigated as a marker of antioxidant properties. The polymorphism at 55 and 192 position known to be associated with PON1 enzyme are also investigated in Egyptian normal and chronic liver patients, in order to elucidate whether such polymorphism has any effect on the enzyme activity, and consequently the state of hepatic affection. Whether routine assay of PON1 activity in chronic liver disease patients can be introduced as a non-invasive clue marker for diagnosis and rating the stage of hepatic affection is another aim of the present work. Methods: We studied 75 patients with chronic liver disease (25 patient with chronic Bilharziasis, 25 patients with chronic hepatitis C, 25 patients with mixed hepatitis C and bilharzial cirrhosis) and 25 apparently healthy controls. Serum paraoxonase activity and levels of the lipid peroxidation marker (serum malondialdhyde) were measured spectrophotomtrically. PON1 genotyping at positions 55 and 192 were analyzed by PCR, restriction fragment length polymorphism and agarose gel electrophoresis. Results: the present work showed that chronic liver disease (viral and/or bilharzial) are associated with elevated oxidative stress (as indicated by increased MDA level) together with reduced PON1-activities, which is regarded as an antioxidant tool. The frequency of investigated polymorphism at 55 and 192 position were found to be of no statistical significance between patients and control groups. The MDA and PON1 values did correlate with standard liver function. Conclusion: The present work could introduce the assay of PON1 activity in the serum as a non-invasive, specific and reliable marker in a trial to assess the state of liver affection in chronic hepatic diseases.