The present study was conducted to report the effect of prenatal and postnatal treatment of lead (Pb) on some antioxidant defense system in cerebrum and cerebellum of dams and of their foeti, histopathological lesions and DNA fragmentation in brain of intoxicated dams. Experiments were carried out on pregnant Wister rats, they were divided into four groups as follows, Group I (pregnant group, n=10) received lead acetate in their drinking water with concentration of 0.1mg / ml from the 0 day of pregnancy till parturition, Group II (pregnant and lactating group, n=10) were treated as that of group I, but lead exposure extended to the lactation period (21 days after parturition). The suckling pups were allowed to suckle their mothers during the exposure period. Group III (lactating group, n=10) were allowed to deliver without any treatment then they were exposed to lead acetate in their drinking water in the same concentration during the lactation period and their pups suckled them till weanling (21 days), Group IV (control group, n=30) were left without any treatment from the 0 day of pregnancy till the end of lactation (21 days). At the end of each exposure period, dams as well as their pups were weighted and sacrificed by decapitation. The brains were obtained and weighed and dissected into two regions, cerebrum and cerebellum. In pups tissue of three littermates was pooled, weighed and homogenized. The obtained results showed that there was a significant(p < 0.05) decrease in the activity of superoxide dismutase, catalase and glutathione in both cerebrum and cerebellum of lead treated rats at the three experimental periods.In addition, a significant elevation of lipid peroxidation was recorded in cerebrum and cerebellum of treated rats and their pups at the three different stages of the experiment was observed. The present data revealed that cerebrum of the treated dams and their pups was more affected than cerebellum. The histopathological examination of cerebrum and cerebellum of treated dams showed marked alterations. DNA fragmentation percent increased while prolactin gene expression showed significant declination especially in pregnancy and lactation group. This study concluded that prenatal and postnatal exposure to Pb induced marked alteration on some antioxidant defense system in cerebrum and cerebellum of dams and of their foeti, marked increase in DNA fragmentation percent in brain of intoxicated dams. Moreover, there was significant declination in prolactin gene expression especially in pregnancy and lactation group.