Niclosamide, as a semisolid pharmaceutical form suitable for external use, was used in 4 different concentrations (0.5%, 1%, 2% & 4%) to paint albino mice tails at different periods before exposure to infection with S. mansoni cercariae. Complete protection (100%) was achieved in all mice painted on the same day, the previous day and 3 days before exposure to cercariae irrespective to the niclosamide concentrations. Neither eggs nor worms were detected. Also, no pathological changes were found in livers, spleens or intestines of those mice. On the other hand, no protection against infection was achieved in mice painted with, 0.5% or 1%, 7 days before exposure to cercariae. Partial protection (25% and 40%) was gained in mice painted with 2% or 4% concentration of the drug respectively. It can be concluded that locally application of niclosamide as an ointment can completely prevent the infection with S. mansoni for three days. So, testing the promising drug for human trials to evaluate its efficacy specially for those at high risk is recommended.