The scope of this study was to determine the effect of gemfibrozil, l-carnitine and their combination on paraoxonase/arylesterase activity, oxidative/anti-oxidative parameters and hepatosteatosis in rabbits on fat-rich diet. The study involved 35 New Zealand albino white rabbits. Animals were equally divided into 5 groups (n=7); group I: control (standard diet), group II: rabbits received only fat-rich diet, group III: rabbits received fat-rich diet plus gemfibrozil (100 mg/kg/day, oral), group IV: rabbits received fat-rich diet plus L-carnitine groups (200 mg/kg/day, oral), and group V: rabbits received fat-rich diet plus the combination of gemfibrozil (100 mg/kg/day, oral) and L-carnitine (200 mg/kg/day, oral) for 9 weeks. The results revealed marked increases in ALT and AST activities in group III (P < 0.05) throughout the experiment and a gradual increase in activities of paraoxonase/arylesterase in group III, IV and V when compared to group I and II (P < 0.05) and a decrease in OSI and TOS levels in group IV and V when compared to group I and II (P < 0.05) over the experimental period. A significant negative correlation between serum OSI and paraoxonase and arylesterase activities in group IV (r=-0.36, P < 0.012 and r=-0.41, P < 0.009, respectively) and V (r=-0.31, P < 0.022 and r=-0.37, P < 0.014, respectively). A similar correlation was determined for liver samples. Changes in paraoxonase and arylesterase activity at 0, 3, 6 and 9 weeks were positivelly correlated with the changes in high density lipoprotein-cholesterol (HDL-C) in group III (r=0.63, P < 0.001 and r=0.57, P < 0.003; respectively). The present study disclosed hepatosteatosis and hyperlipidemi due to fat-rich diet in rabbits, and treatment of gemfibrozil is required in order to increase PON1 activity.