Lead (Pb) is a hazardous substance due to its ability to bioaccumulate in living organisms; therefore, lead is highly detrimental to human health and the environment. The objective of this study was to examine the histopathological effects of lead acetate treatment on liver and kidney tissues in mice. METHODS: Mice (n = 20, 10 per group) were randomly assigned to either a control group (standard laboratory conditions) or lead acetate-treated group (50 mg/kg) for 30 days. All mice were housed under controlled temperature and light-cycle conditions and provided standard chow and tap water. After the experimental period, the liver and kidney tissues were removed and immediately immersed in 10% neutral buffered formalin (NBF). The tissues were embedded in paraffin blocks and sectioned at 5 µm. The sections were stained using Hematoxylin-Eosin, Periodic Acid-Schiff, and silver stains. Results obtained from all examinations indicated alterations in tissue structure and metabolism. Both liver and kidney tissues demonstrated destruction of normal architecture and degenerative cytoplasmic changes. Kidney tissues showed necrotic renal tubular cells, degenerative changes in the epithelial lining of the renal tubules, and deposition of cellular debris within the glomeruli. PAS staining indicated a significant reduction in glycogen content within hepatic cells. Tissue injury was also evident due to the disorganized appearance of tissues and fragmentation of extracellular matrix components, which were assessed using silver stains. To summarize, lead acetate induced histopathological and histochemical changes in liver and kidney tissues associated with disruption of normal organ structure and function.