High Mobility Group B1 (HMGB1) is a ubiquitous and highly conserved nonhistone DNA-binding protein in eukaryotic cells. In most cells HMGB1 is located in the nucleus, where it acts as an architectural protein that can bend and supercoil DNA. HMGB1 proteins are organized into two DNA-binding domains (named A-box and B-box), and a negatively charged C-terminus. Besides its nuclear function, HMGB1 was recently discovered to be a potent cytokine that mediates the response to infection, injury and inflammation. In this respect, antibodies against HMGB1 were able to completely clear sepsis in animals with high levels of bacterial infection. The role of HMGB1 as a pro-inflammatory protein is partially possible because it is actively secreted by activated immune cells after being acetylated by protein acetyltransferases. In the present work we generated polyclonal antibodies against schistosome (SmHMGB1) and human (hHMGB1) HMGB1 proteins in order to carry out immunological assays. We showed by Western Blot that S. mansoni egg homogenates contained SmHMGB1. Macrophages from peritoneal wash of animals infected with S. mansoni also produced HMGB1, as shown by immunocytochemistry. Futhermore, Liver and spleen cells from normal and infected mice also contained HMGB1 in the nucleus and cytoplasm. We further showed that SmHMGB1 and hHMGB1 were both acetylated by schistosome acetyltransferases SmGCN5 and SmCBP and that HMGB1 proteins were secreted by the infectious agent (adult schistosomes and eggs) and by the host (mice macrophages). By the fact that HMGB1 proteins are being considered efficacious therapeutic targets for several chronic inflammatory diseases, we believe that administration of antibodies raised against HMGB1 proteins from the parasite and the host may block the formation of inflammation-mediated granuloma. In this respect, we are currently initiating HMGB1 antibody treatment in mice infected with S. mansoni.