Résumé : Chagas disease is one of the most common parasitic infections in Latin America, which istransmitted by hematophagous triatomine bugs, of which Rhodnius prolixus is the vector prototype forthe study of this disease. The protozoan parasite Trypanosoma cruzi, the etiologic agent of this disease,is transmitted by the vector to humans through the bite wound or mucosa. The passage of the parasitethrough the digestive tract of its vector constitutes a key step in its developmental cycle. Herewith,by a using high-throughput proteomic tool in order to characterize the midgut proteome of R. prolixus,we describe a set of functional groups of proteins, as well as the biological processes in which theyare involved. This is the first proteomic analysis showing an elaborated hematophagy machineryinvolved in the digestion of blood, among which, several families of proteases have been characterized.The evaluation of the activity of cathepsin D proteases in the anterior part of the digestive tract ofthe insect suggested the existence of a proteolytic activity within this compartment, suggesting thatdigestion occurs early in this compartment. Moreover, several heat shock proteins, blood clottinginhibitors, and a powerful antioxidant enzyme machinery against reactive oxygen species (ROS) andcell detoxification have been identified. Highlighting the complexity and importance of the digestivephysiology of insects could be a starting point for the selection of new targets for innovative controlstrategies of Chagas disease.