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Objective: To study the prophylactic effect of artesunate against the infection of Schistosoma mansoni in mice and its optimal scheme for preventing schistosomiasis mansoni., Methods: BALB/c mice were infected by tail dipping method with S. mansoni cercariae. Mice were administered orally with artesunate at different developmental stage of the parasite, with different regimens. The reduction rates of total and female worms, the number of eggs in the liver and intestine, and the fecundity were calculated and treated statistically., Results: The optimal dosage of artesunate to prevent murine schistosomiasis was 300 mg/kg. The parasite was found to be especially susceptible to artesunate in its schistosomula stage of 14 and 21 d after infection, resulting in worm reduction rate of 84% and 93% respectively compared with control. High protection was reached with worm reduction rate of 99% by the regimens of 300 mg/kg once a week for 4 consecutive weeks beginning 14 d after infection. The fecundity was significantly suppressed, suggesting that the drug inhibited sexual maturation of female worms. The effective protection could also be gained with prolonged interval time of two weeks with worm reduction rate of 97% and 96% beginning 14 or 21 d after infection., Conclusion: Artesunate kills schistosomula and reduces the fecundity of females effectively, the infected mice do not develop schistosomiasis mansoni when treated with artesunate. It's proposed that an optimal scheme for field use be the first administration 14 or 21 days after infection with 1 or 2 weeks interval.