Purpose: To evaluate the anti-trypanosomal effect of secnidazole (SEC) in vitro and in vivo. Methods: The dose-response effect of SEC in Trypanosoma b. brucei infected rats was evaluated in five groups of rats (n = 5). Group A was infected but untreated; B was given diminazene aceturate (DA) (3.5 mg/kg) intraperitoneally, while groups C, D and E received orally 400, 800 and 1600 mg/kg of SEC, respectively. The effect of a combination therapy of SEC and DA was studied in 7 groups of rats (n =5). Group 1 was infected but untreated; groups 2 – 7 were treated with DA (3.5 mg/kg), while groups 3 – 7 received in addition to DA, increasing double doses of SEC (50 – 800 mg/kg).Results: The MIC of SEC and DA were 1.4 and 0.0021 mg/ml respectively. SEC dose-dependently and significantly (p < 0.05) lowered parasitemia from day 2 post-treatment (PT) compared with infected untreated rats. Parasitemia was cleared 3 days PT in all combination groups and 5 days PT in DA group. Relapse of infection occurred in Group 2, 13 days PT, and 16 and 27 days PT in Groups 3 and 4 respectively. There was no relapse of infection in Groups 5 – 7 up to 70 days PT.Conclusion: These results suggest that SEC possesses some degree of anti-trypanosomal effect, and that combination therapy of SEC and DA was superior to DA alone.Keywords: Trypanosoma, Secnidazole, Diminazene aceturate, Anti-trypanosomal, Combination therapy