Abstract: The Trypanosoma cruzi trans-sialidases (TcTS) are able to cut and transfer sialic acid from the host cell to the parasite surface and are important molecules on this interaction. Trypanosoma rangeli is a non-pathogenic parasite to mammal, that posses an unknown life cicle in this host, and it has similar genes to TS family members in the genome, however, with no catalytic activity. Once TS are crucial molecules involved in parasite-host cell interaction in the pathogenic parasite, and the absence of TS activity is pointed as one of the reasons of its inability capacity of infecting and surviving in mammals cells, the aim of this work was to study the roll of TS in the host-parasite interaction using T. rangeli expressing an active TcTS (T. rangeli TcTS). After transfection and assessment of protein activity, 4° and 5° instar nymphs of Rhodnius prolixus were infected by intracelomic inoculation of T. rangeli wild type and T. rangeli TcTS epimastigote forms. A statistically significant difference was observed in the number of salivary gland infected for T. rangeli wild type (92%) and for T. rangeli TcTS (16%) at six weeks p.i.. Parasitemia of BALB/c mice and C57BL/6 infected by T. rangeli TcTS showed no difference from mice infected with non-transfected parasites. For in vitro infection assays with Vero cells, T. rangeli TcTS presented higher infection rates when compared with T. rangeli wild type, but no indication of intracellular division was detected for these parasites up to 120 hours. Despite not altering the parasitemia in mice, our results indicate that TcTS expressed by T. rangeli may be responsible for changes on the interaction between vector-parasite and cell-parasite by reducing the ability to penetrate on R. prolixus salivary glands and facilitating cell entry in vitro.