Abstract: Schistosomiasis is a chronic disease that infects over 200 million people worldwide. The treatment and control of schistosomiasis largely depends on a single drug, praziquantel that might result in emergence of drug resistant parasites. Consequently, developing new drugs is a true need. The anti-malarial drug mefloquine has shown schistosomicidal activity. The aim of this study was to assess the effect of mefloquine against adult S. mansoni using in vitro approach. Ten laboratory bred mice were infected with S. mansoni cercariae. After 56 days, mice were sacrificed and adult Schistosoma were collected by perfusion. The in vitro approach consisted of placing adult Schistosoma worms in culture plates containing 100, 10 and 1 μg mL-1 mefloquine and incubating the plates at 37°C for 24 h. The length and maximum width of adult Schistosoma were measured and LC50 and LC90 of mefloquine and praziquantel were calculated. The results showed that the LC50 for mefloquine and praziquantel were 3.961 and 6.675 μg mL-1, respectively. The LC90 for mefloquine was 7.332 μg mL-1 while that of praziquantel was 8.695 μg mL-1. A statistically significant reduction in length and maximum width in adult worms treated with mefloquine was observed. Mefloquine exerted promising in vitro effects on adult S. mansoni worms.