Lead is one of the most well-known naturally occurring environmental heavy metals. This experimental study was designed to evaluate lead induced toxic effects on hepatocytes and lobular architecture as judged microscopically. Material and Methods: This study was conducted in anatomy department, Benha faculty of medicine, Benha University, Egypt from May to October 2013 on 30 normal adult albino rats divided into 3 groups; one control and 2 experimental groups. The experimental groups were given 0.13% lead acetate solution in drinking water for 4 and 8 weeks, respectively. Animals were scarified and livers were removed and used to identify microscopic changes. Specimens were stained with Hematoxylin and eosin, with Masson trichrome stain for study of fibrous tissue and with periodic acid shiff's (PAS) to study the glycogen content . Other specimens were prepared for ultrastructural study. Results: Mild lymphocytic infiltration, vacuolar degeneration and mild increase of periportal fibrosis with mild depletion of glycogen content and partial disappearance of glycogen vacuoles were reported in animals received contaminated water for 4 weeks. Animals maintained for 8 weeks on contaminated water showed hepatic changes in the form of abundant lymphocytic infiltration, increased cellular polymorphism, pyknotic nuclei and areas of cell necrosis with evident moderate periportal fibrosis and marked vacuolar degeneration associated with marked depletion of glycogen content. Ultrastructural study revealed mitochondrial edema, appearance of interstitial inflammatory cells, and appearance of scattered variable sized lead electron-dense inclusion bodies. Conclusion: It could be concluded that chronic exposure to lead imposes a potent toxic effect on liver cells manifested as glycogen depletion, cellular infiltration and liver architecture in the form of initiation of periportal fibrosis that may progress to liver cirrhosis.