In order to investigate the pathogencity, histopathological changes and clinical signs in white Swiss mice infected intraperitoneally with 3 different strains (NC-5, BPA4 and Nc1) of Neospora caninum, mice were kept under observation for 90 days after infection. The samples (blood, brain, skeletal muscle and heart) were collected at different times for diagnosis of the parasite by using Tissue culture (Vero cell, Real Time PCR and Histological sections) with observation of the clinical signs. The results showed clinical signs which manifested coat roughening, body hunching, weight loss, head tilting and impaired movement which were variable according to strain. The earlier signs appear in mice infected with NC-5 and BPA4 when comparison with mice infected with Nc1, the result of propagation of parasite from the organs collected from infected mice showed variation in Cyto Pathic Effect (CPE) in vero cell, the CPE appear in the 3^rd passage in BPA4 and NC-5 when comparison withNc1 (4^th) passage with higher titer in BPA4 when compared with other strains, the parasite appear in the blood sample in vero cell after 14 days of infected mice with NC-5 strain, the Real Time PCR result showed appearance of positive reaction in the infected cells culture infected with NC-5 and BPA4 strains. The histopathological changes appear presence of tissue cyst with prevascular cuffing and aggregation of glial cell, loss of Neuropil and infiltration of mononuclear cell in brain, the skeletal muscle showed presence of lymphocytes and plasma cell with some macrophage, the heart section showed heavy infiltration by inflammatory cells (plasma cell and lymphocytes), this histopathological changes appear delayed when compared with tissue culture and Real Time PCR.