Parasitologyl and Pathology2 Ain Shams* and Benha Faculties of Medicine Abstract The effect of oral administration of CsA (50 mg / kg) as single dose, 2 days post-infection and as three doses, one day before, on day of infection and on day 1 after infection was assessed in murine S.mansoni regarding its effect on: worm burden, female fecundity, % protection, histopathological changes in liver and large intestine and on the immuno-regulatory system including antibody-mediated mechanism by IgE estimation using immuno-radiometric assay (IRMA). The results showed parasitic damage in form of: stunted growth, appearance of surface protuberances and irregularities specially 70 days post-three doses. Reduction in worm burden, female fecundity, as well as the number and size of liver granulomata with the appearance of well circumscribed ones in infected, treated and challenged groups denoting early healing. IgE levels were higher in CsA treated groups than in infection control specially after using triple doses that indicated direct schistosomicidal and prophylactic effects for the drug after its administration before, on day of infection and on day 1 after infection.