Laboratory investigations were carried out to study the effect of two protease inhibitorson the transmission of W. bancrofti filarial by Culex pipiens and to studythe susceptibility interaction between filaria and protease inhibitors. The resultsobtained revealed that, infection rates were variable among untreated and treatedsymbiotic and aposymbiotic Cx. pipiens females resulted from third instar larvaetreated with E-64 and EDTA. The survival rate was variable among untreated andtreated symbiotic and aposymbiotic females resulted from third instar larvae treatedwith E-64 and EDTA. Protease inhibitor (E-64) caused inhibition of the parasitedevelopment and transmission by means of ceasing catalytic activity- responsiblefor parasite migration-caused by parasitic larval stages inside the mosquito vector.