Schistosomiasis is one of the most significant parasites especially in tropics and subtropics.The only recognized drug used for treatment of all species of Schistosoma is praziquantel (PZQ).Worries about drug resistance motivated the quest for novel drug sources. Genistein, which is anatural product present in soybeans, was assessed for its antischistosomal effects in experimentallySchistosoma mansoni (S. mansoni) infected mice either solely or in association with PZQ.All groups that were infected subjected to portal and mesenteric veins perfusion, evaluation ofworm burden, liver and intestinal ova count, and the oogram. Moreover, ultrastructural changesin the worm’s tegument and interleukin IL-1β (IL-1β) levels in infected mice were also assessed.There were significant reductions in the total worm number and egg load of liver and intestinewith significant decrease in immature and mature eggs in all groups received treatment in comparisonwith the infected non treated control one. Tegument of adult worms exposed to genisteinexhibited distortion of suckers and erosions with loss of tubercles and spines. There was decreasein the IL-1β level in all treated groups. The best results, in all parameters, were given bycombined (genistein & PZQ) treatment. Genistein possessed moderate activity against S. mansoniadults and considered as a good adjuvant to PZQ.