Camel Trypanosomiasis is one of the most significant illnesses influencing the livestock economic development. The present study reports observations of histological and immunohistochemical alterations of Trypanosoma evansi infection in the liver samples of camels (Camelus dromedarius) from Al-Madinah district in Saudi Arabia . Liver of camels showed presence of red blood cells among the hepatic cells, infiltration of connective and fibrous tissue between the liver’s lobules, and a reduced number of hepatic cells. Upon Masson trichrome staining the infected liver showed elevated deposition of thick collagen fibers that were conspicuously stained blue. Immunohistochemical study of the -SMApositive cells in the T. evansi infected camels also exhibited considerable growth of the brownish cells between the sinusoidal walls and around the portal area. Moreover, increase numbers of -SMA-positive cells in the tissue zone around the portal vein, artery, and bile duct branches were observed. Overall, the infection stimulates hepatic CD8+ and CD4+ T cells in the liver, which is a well-known component of the immune response cascade, according to the study. The acquisition of milk, meat, and other products is crucial for camels. Therefore, it is essential to examine the camels’ health, risks, and pathological effect of related diseases.