The objective of this study was to evaluate the antischistosomal activity of the aqueous extract of Sida pilosa Retz (Malvaceae) on Schistosoma mansoni-infected mice and its toxicity profile. Sixty days post infection, animals were treated orally with the extract at 40, 80 and 160 mg/kg/day, for fourteen consecutive days. Unique administration of doses ranging from 4 to 20g/kg were used to assess acute toxicity while doses of 400, 800 and 1600 mg/kg/day for 8 weeks were used for sub-acute toxicity. One week after treatment, comparisons of body, liver and spleen weights, egg load and worm recovery were carried out between untreated and treated groups. Treatment with S. pilosa aqueous extract resulted in a significant reduction in egg-laying of at least 82% and in worms recovering of at least 88%. A significant reduction of hepatomegaly and splenomegaly (p < 0.001) were also seen in all treated-animals. The LD50 of S. pilosa aqueous extract was greater than 20g/kg and neither haematological nor biochemical parameters were modified after administration of the extract for eight weeks. These results indicate that S. pilosa aqueous extract exhibits antischitosomal activity in S.mansoni-infected mice and is toxicological safe.