The aim of the current study is to follow up Trypanosoma evansi infection in experimentally infected mice by the parasitological and molecular assays. Also, the pathological alterations in different tissues associated with the infection throughout the course of disease were investigated. Forty two male and forty two female Swiss mice were injected I/P by 102 trypanosomes and five mice for each group were kept as non infected control. The course of infection was followed up by direct microscopic examination and PCR assay for T. evansi RoTat 1.2 VSG gene. Pathological changes were also estimated through the disease progression by examination of thin sections from formalin fixed tissues and staining with haematoxylin and eosin. Results revealed earlier detection of T. evansi in mice blood by PCR at 24 h post-infection while direct microscopic examination revealed that the pre-patent period was five days. During the chronic course of the disease, when the parasite disappeared from the blood by direct microscopic examination, PCR assay gave positive signals for the parasitic DNA in the blood. Histopathological examination revealed that T. evansi induced destructive irreversible damage of the mice vital organs (kidneys, liver, spleen, brain and testes) especially in chronic infection and lead to death of the animals with progression of the disease. It also affects animals' fertility. It induces degenerative changes in the testes and seminiferous tubules.