Trypanosomosis is a disease of medical and veterinary importance, mainly distributed in tropical areas around the world. Some Trypanosoma species are typically pathogenic for animals (Trypanosoma vivax, T. congolense, T. evansi etc), and the others are zoonotic, such as the agents of sleeping sickness in Africa, or Chagas disease in Latin America. On top of these “typical” human trypanosomoses, there is an increasing number of reports of atypical human infections by animal trypanosomes, such as T. evansi, Trypanosoma lewisi or Trypanosoma lewisi-like. T. lewisi is commensal trypanosome of rats; it is a worldwide distributed stercorarian parasite transmitted by fleas. Although, non-pathogenic in rats, several clinical cases of T. lewisi-like infections occurred in humans, amongst which one was recently described in an infant in Thailand. In order to explore efficient trypanocidal mechanisms and to propose a way to monitor the infection by T. lewisi in laboratory rat colonies, attempts were made to treat experimentally infected rats using the most common veterinary trypanocidal drugs. Diminazen aceturate (14 and 28 mg/kg), isometamidium chloride (2 and 4 mg/kg), suramine (20 & 40 mg/kg), quinapyramine sulfate and chloride (8.3 and 16.6 mg/kg) and cymelarsan (0.5 and 1 mg/kg) were intramuscularly injected to groups of 3 experimentally infected Wistar rats, during a stable parasitaemic phase. All treatments at all doses failed to clear parasites from rat's blood. In subsequent mixed experimental infections of 3 rats with T. evansi & T. lewisi, daily peroral administration of 100mg/Kg of fexinidazole cleared T. evansi from the blood within 24 hours while T. lewisi kept its development despite the treatments. Results are discussed and further studies suggested. Because of its potential as an emerging parasite in humans, identifying efficient trypanocides against T. lewisi is required.