INTRODUCTION: The adult worm of Schistosoma mansoni has a peculiar and different habitat from other intestinal helminths, the vascular lumen. Despite this long-standing knowledge, there is still limited information about the interaction between adult worm and endothelial cells. Furthermore, the possible role that antioxidant agents secreted by these cells have on the infection or during the treatment with praziquantel (PZQ), the only drug approved in Brazil to treat schistosomiasis, is not well known. METHODS: Names of genes, enzymes and substrates used in this abstract will be presented in a coded form to keep confidentiality because of its sensitive information for innovation. Adult worms were obtained from infected mice by perfusion through the portal system. Then, Human Umbilical Vein Endothelial Cells (HUVEC) were cultured and challenged with a pair of adult S. mansoni worms, and with PZQ for 1, 3 or 6h. After the challenge, RNA extraction was performed using Trizol, followed by qPCR for five different antioxidant genes (αOX-A, -B, -C, -D, -E). In order to determine the ability of adult worms to survive under oxidative stress, adult worms were cultivated with HUVEC in the presence of an oxidizing agent (OX). RESULTS: PZQ challenge was able to induce the expression of αOX-A and αOX-B antioxidant genes in HUVEC. Regarding the effect of adult worm in HUVEC, it was interesting to note that adult worms were not able to induce or suppress any antioxidant genes, except for αOX-E, which had its expression significantly increased in HUVEC cells after 6 hours of exposure to a couple of adult worms. The oxidizing agent OX was able to kill adult worms of S. mansoni, however this effected was reversed when adult worms were incubated with OX in the presence of HUVEC, suggesting that endothelial cells could help protect the worm against attack by oxidizing agents. Moreover, when challenging adult worms with OX in the presence of the antioxidant protein αOX-E we observed an increased ability to survive even in high concentration of OX, like what was observed when worms were incubated with HUVECs and OX. CONCLUSION: Adult worm of S. mansoni induces expression of αOX-E in HUVEC, which leads to a protective environment that could help survival and maintenance of adult worms in the vascular lumen. This new information may help new approaches for the treatment of schistosomiasis.