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African trypanosomiasis is a parasitic disease that affects both humans and animals. This study investigated the antitrypanosomal activities of crude and an alkaloidal fraction of Diospyros mespiliformis in Trypanosoma evansi – infected rats. A total of twenty-one (21) albino rats were infected with Trypanosoma evansi and grouped into seven (A-G) of 3 rats each. Group A serve as normal control, groups B and C were given 0.2 ml normal saline/kg BW and 3.5 mg/kg BW diminazene aceturate respectively, groups D and E were treated with 100 and 200 mg/kg BW alkaloidal while groups E and F received crude extract at 200 and 400 mg/kg respectively for twelve days. Results revealed that both crude and an alkaloidal fraction of D. mespiliformis exhibited significant (p<0.05) dose-dependent antitrypanosomal activities. The crude extract exhibited 54.55±3.04 % (200 mg/kg BW) and 66.02±5.03 (200 mg/kg BW) curative effect while the alkaloidal fraction exhibited better antitrypanosomal activities with 68.68±2.34 % and 70.87±2.93 curative effect at 100 and 200 mg/kg respectively. Furthermore, the crude extract prolonged the survival of the animals to 19.02±2.06 (200 mg/kg BW) and 22.90±3.78 (400 mg/kg BW) while the alkaloidal fraction at 100 and 200 mg/kg prolonged the survival of the mice to 23.45±1.24 and 29.34±3.45 days respectively and improved the body weight gain of the animals when compared with the non-treated control (13.24±1.33 days). In conclusion, the leaves of Diospyros mespiliformis could be employed for the treatment of T. evansi infection as an alternative to conventional medicines that are besieged with undesirable properties