To investigate the toxic effects of fenitrothion and lead acetate on dams and their pups during lactation period. Twenty four female pregnant albino rats were divided into four groups, first group as control, second group received orally (80 mg/kg B.wt fenitrothion), third group received orally(60 mg/kg B.wt lead acetate), fourth group received orally (80 mg/kg fenitrothion B.wt plus 60 mg/kg B.wt lead acetate). The results indicated that decrease in body weight of pups for all treated groups compared to control group. The activity of ALT, AST and GGT increased in mothers serum, increased levels of creatinine and urea in mothers serum. Increased in oxidative stress, indicated by increased the level of MDA of liver homogenate for mothers and their pups, and decrease in the antioxidant enzymes, activities (GSH, GST and SOD) in liver homogenate for mothers and pups. Decrease ChE activity in mothers serum and its brain homogenate for mothers and pups. This result consistent histopathological changes were found in the liver, kidney, spleen, pancreas and brain of mothers and liver, kidney, spleen and brain of pups. The results suggested that the transfer of fenitrothion and lead acetate through the mother milk has resulted in oxidative stress and biochemical and histopathological alterations in the suckling pups. Also the combination between lead acetate and fenitrothion consider synergistic effects either on dams or pups.