Schistosomiasis as a neglected disease is second to malaria in its adverse effect to public health and socioeconomics impact in the tropics and subtropical of the developing countries where 90% of 249 million people affected are found in Africa. Mwea irrigation scheme in Kenya is infested with Biomphalaria spp. and the research set out to find their susceptibility to Schistosoma mansoni miracidia. Vector snails' samples were taken from endemic region of Mwea irrigation farmlands and were morphological identified and then cultured. The miracidia exposed snails were transferred into aquaria and after four weeks of exposure they were examined for cercaria shedding twice every week under direct sunlight illumination. It was found that Mwea irrigation scheme was dominantly infested by Biomphalaria pfeifferi. From the morphological parameters of B. pfeifferi it was found that there was no statistical difference in physical characteristics between resistant and susceptible populations. The results in this study showed that the mean value of infection for the Field, F1 and F2 snail samples were 36.6 ± 3.72, 1.93 ± 1.46, 0.36 ± 0.049 respectively and the infection rate decreased from the field snail samples through F2 snail samples. This suggested that the exhibited resistant traits may be due to snail internal defense mechanisms rather than morphological characteristics and this could be thought that the various levels of B. pfeifferi susceptibility to S. mansoni is attributed to genetic variations within a population. Finally, the findings generated in this study, under laboratory condition, suggest that S. mansoni resistant population of B. pfeifferi can be isolated and mass reared with a view of diversifying biological control measures of the vector in Mwea irrigation scheme in Kenya.