Central nervous system diseases are one of the disabilities and death causes of livestock animals in the worldwide.Our harmony of its pathobiology has increased fundamentally at recent time.The present work aimed to Detection GFAP and CD65 expression correlated with microscopically lesions in the sheep brain in Mosul city.32 samples of ovine brain were collected during the period from December 2022-February 2023,the gross lesionsrepresentedbycirculatory disturbances(hemorrhage and congestion ),parasitic infection, disturbance of growth and brain pigmentation. Affected samples were gathered andpreparedforroutinhistopathologyandimmunohistochemistryexaminations.Incontrast,theinflammationfindingwas31.25%representedbyinfiltrationofmononuclearanmultinucleatedinflammatory cell,circulatorydisturbancewith21.87%percent,disturbanceofgrowth which accounted 12.5%, parasitic infection with a 15.62% percent and pigmentation with 6.25% percent and finally necrosis with 12.5%.Results of histological examinations revealed perivascular edema with congestion in the meningeal blood vessels, severe congestion in the cerebral and cerebellar veins,aswell as infiltration of mononuclear and multinucleated inflammatory cells with condensation of inflammatory cells around the blood vessels. In addition,vacuolar degeneration and gliosis with the presence of phagocytic cells with foamycytoplasmand suppurative encephalitis, as well as presence of larval stages of Toxoplasmagondii, Sarcocystosis parasites in the brain tissue andHydatid cysts of Echinococcus granulosus in the cerebellum. Reproducible function of glia and neurons of ovinebrainisfundamental forcellularchangesstudyin neurodegenerative disease. Moreover, immunohistochemistry represented by CD65 as a minor E-selectin lingad andGlial fibrillary acidic protein (GFAP) as a candidate for future counting of cells and scoring as a mild, moderate and sever lesion.We concluded that ovine are exposed to different types ofneurodegenerative diseases.Immunohistochemistry technique can beusedas a biomarker for the severity of the disease and molecular biology techniques should be done for abnormal protein expression