The therapeutic effects of praziquantel (PZQ) against a Schistosoma mansoni isolate derived from Nectomys squamipes (isolate R) and a susceptible isolate (BH) were analyzed in Swiss mice by fecal egg counting, adult worm reduction and oogram pattern. Infected mice were orally administrated with 62.5mg/kg (group 1), 125mg/kg (group 2), 250mg/kg (group 3) and 500mg/kg (group 4), each dose divided over 3 days (49, 50 and 51 days after infection). The data were analyzed using one-way analysis of variance (ANOVA). In regard to isolate R, no fecal eggs were observed with 250 mg/Kg and 500 mg/kg (p<0.05), whereas BH excretion reached zero with all doses. Mean worm burden reduction was significantly (p<0.05) higher at the two highest concentrations, regardless of isolate. At 62.5mg/kg, the percentage of immature eggs varied from 17% (isolate R) to 38% (isolate BH). At 125 mg/kg, the percentage of immature eggs varied from 20% (isolate R) to 16% (isolate BH). At 250 mg/kg, immature eggs dropped significantly to 1% (isolate R) and 4% (isolate BH). At 500 mg/kg, no immature eggs were found in isolate R, whereas in BH was 8%. No dosage significantly (p>0.05) affected the percentage of mature eggs, regardless of isolate. There was a large increase (p<0.001) in the percentages of dead eggs in all treated groups of 62% and 64% in groups 3 and 4, respectively (isolate R). The percentage of dead eggs rose from 34% (group 1) to 58% (group 3) in isolate BH. Although group 4 showed lowest increase in the percentage of dead eggs (46%), it was higher (p<0.001) compared to the 8% in the control. Our findings indicate that the wild isolate from N. squamipes is susceptible to PZQ.