Murine schistosomiasis represented a good lab model of granulomatous hypersensitivity reaction which could be elicited by S. mansoni eggs trapped in the host tissues which might lead to liver fibrosis. Pentoxifylline (PTX) is an immunomodulatory and antifibrotic substance. The present investigation aimed to study the action of PTX (4 weeks post infection) either alone or combined with PZQ (7 wk PI) on fibrosis developed from murine hepatic schistosomal granulomatous reaction. The experiments were carried out on naïve C75BL/6 mice that were divided into three groups. Two control groups were used one without infection (normal) and the other was infected without treatment. Mice were sacrificed 12 weeks post infection.       PTX treatment alone caused a partial toxic effect on worm burden; egg count; and ameliorated the liver functions. But, it increased immature and dead eggs, while it decreased the mature ones. PZQ administration alone or in combination with PTX showed a highly significant reduction in worm burden, egg count, disappearance of immature egg stage and a high increase in dead eggs. Also, it caused a highly significant reduction in granuloma count, diameter and ameliorated liver functions.  In conclusion,according to the parasitological, histopathological and biochemical criteria of the present study, PTX can be successfully introduced into antischistosomal therapy as a potent antifibrotic agent with immunomodulatory properties in combination with PZQ.