Longitudinal research on biochemical, haematological and histopathological changes in calves experimentally infected with T.vivax isolate from tsetse and non tsetse infested areas of North West Ethiopia after treatment with diminazene aceturate and Isometamidium chloride were conducted. Calves were grouped in to7 groups of 6 animals per group and then challenged by T. vivax at a dose of 1x106parasites/ml intravenously (group 1&2 challenged with isolate from tsetse area, group 3,4,5,6 with isolate from non tsetse area) and group 7(control animals) were received saline water. 14 days post infection calves in group1, group3 and group5 were treated with diminazene aceturate at a dose rate of 7mg/kg body weight and group2, group4 and group6 were treated with Isometamidium chloride at a dose rate of 1mg/kg body weight IM. All trypanosome-inoculated cattle developed acute form of trypanosomosis following the detection of parasitemia in the blood of infected calves. There was variable degree of reduction in mean PCV, Hb concentration and RBC after infection. After treatment all infected groups has resulted in significant improvements in which PCV, Hb concentration and total RBC counts became similar to the pre-infection values for group1 and group2. There was significant reduction in serum glucose, total protein and cholesterol and significant increase in serum enzymes in all challenged groups. After treatment all groups has resulted in significant improvements in the values which were become equivalent to or better than the pre-infection measurements. Gross and histopathological changes were observed in different tissues of calves after treatment with diminazene aceturate and Isometamidium chloride in all groups of calves which were highlyrnxivrnsignificant in calves infected with isolate from non tsetse area. In conclussion the result of the current experiment revealed that there were improvement after treatment but differences in haematological, biochemical and pathological parameters remained significant in all groups of calves treated with both drugs in comparison to the non-infected groups. So trypanocidal drugs which can not only result in clinical cure but also cause a better improvement in pathophysiological parameters should be developed.rnKey words: Biochemical changes, haematological changes, Pathological changes, Trypanocidal drugs, TT, NT