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The liver of reptiles is considered an important study model for the interaction between environment and hepatic tissue. Little is known about the histology of the liver of reptiles. The aim of the current study was to elucidate the histological architecture of the liver of the Nile monitor (Varanus niloticus). Liver fragments from the Nile monitor were collected in the summer season and processed for the light and electron microscopy. The liver of the Nile monitor was bi-lobed and the right lobe was found to be larger than the left lobe. Histological examination revealed indistinct lobulation of the liver, and the central vein, sinusoids and portal area were haphazardly organized. The hepatic parenchyma consisted of hepatocytes arranged in glandular-like alveoli or tubules separated by a network of twisted capillary sinusoids. The hepatocytes were polyhedral in shape with vacuolated cytoplasm and the nucleus was single rounded, eccentric, large and vesicular with a distinct nucleolus. The hepatocytes contained numerous lipid droplets, abundant glycogen granules and well-developed RER and mitochondria. The hepatocytes appeared to secrete into the bile canaliculi through the disintegration of their dark cytoplasm into the bile canaliculi. The space of Disse separating between the hepatocytes and sinusoids contained many recesses. The portal area contained branches of the portal vein, hepatic artery, bile duct and lymphatic vessels embedded in a connective tissue. Some non-parenchymal cells were described such as Kupffer cells, heterophils, melano-macrophages, intercalated cells, myofibroblasts in addition to the endothelium of the sinusoids. This is the first report about the histological structure of the liver of the Egyptian Nile monitor. The result presented here should be considered a baseline knowledge to compare with the pathological affections of the liver in this species.