This study investigated the protective role of lactoferrin (LF) against lead acetate poisoning in female albino rats (Rattus norvegicus). Four equal groups of animals (6 rats/group) were treated orally/daily by gastric tube for eight weeks. The first group was the control group, the second group received LF (10 mg/kg of body weight), the third group received lead acetate (100 mg/kg of body weight), and the fourth group received both LF and lead acetate with the same doses. After eight weeks, blood and tissue samples were taken for hematological, biochemical and histological analyses. The results showed that lead exposure induced significant elevations (P<0.05) in the activity of plasma alanine aminotransferase and aspartate aminotransferase, plasma creatinine concentration, plasma lead level, hepatic cytochrome P450, and the brain malondialdehyde. Brain superoxide dismutase activity was reduced significantly (P<0.05), in response to the lead toxicity. Lead acetate caused many pathological changes in the liver, brain, and kidneys tissues. Severe DNA fragmentation in the brain tissue was observed after lead treatment. On the other hand, LF was found to modulate significantly (P<0.05) the deteriorations in most parameters under investigation. In conclusion, these data suggest that LF has a protective function in the molecular and histological processes causing neurodegeneration, as well as renal and hepatocyte injury induced by lead.