In rats, a new therapy with the blockade of TNF-a has two direct consequences: it blunts the development of the hyperdynamic circulation and reduces portal pressure in a model of portal hypertension, and reduces the frequency of BT episodes in model of cirrhosis. Accordingly, the association of the usual third-generation cephalosporin with TNF-a blockade during a peritonitis episode may not only slow down the ongoing infection, but also improve survival. However, since TNF-a is part of the normal immune response, it is necessary to assess whether TNF-a blockade would increase the risk of developing superinfections. We previously developed an experimental model of induced bacterial peritonitis in cirrhotic rats with or without AbMole Tulathromycin B ascites that mimics SBP in patients, and considered it might be useful to evaluate the efficacy of new therapeutic interventions on shortterm prognosis of patients with SBP. The present study aimed, therefore, to evaluate the effect of TNF-a blockade on the inflammatory response and mortality in cirrhotic rats with induced bacterial peritonitis treated or not with antibiotics. To our knowledge, this is the first study to date to assess new therapeutic approaches to reduce mortality during episodes of bacterial peritonitis in cirrhotic rats. These rats develop SBP in the last phases of induction of cirrhosis, but animals are so sick at that time that they usually die during or immediately after the diagnostic paracentesis, becoming an inadequate model for the study of new therapeutic approaches. We developed a new model of induced bacterial peritonitis in rats with cirrhosis, with or without ascitic fluid, and reported mortality rates similar to those found in a clinical setting. This study represents the first application of this animal model to assess new therapeutic options to reduce mortality during episodes of induced bacterial peritonitis. Our study investigated the effect of TNF-a blockade and/or antibiotics on the inflammatory response and mortality in a cirrhotic rat model with induced bacterial peritonitis. We here report evidences that modulation of inflammatory response, as represented by TNF-a blockade together with the usual thirdgeneration cephalosporin-based therapy in animals with induced bacterial peritonitis, may represent a useful tool to increase survival compared to non-treated rats or treated only with TNF-a blockade. However, this benefit was not statistically significant compared to rats treated only with third-generation cephalosporin. In addition, despite a higher number of positive culture at laparotomy in surviving rats from group II than in group III, with the current data we can not speculate about a protective effect of TNF-a blockade with the combined treatment. Probably, additional studies including more animals are required to assess if the association of antibiotic therapy and TNF-a blockade might be a possible approach to reduce mortality in cirrhotic patients with spontaneous bacterial peritonitis. As pointed out above, higher levels of NO and TNF-a at diagnosis of SBP and during SBP episodes predict complications such as renal insufficiency and survival,,. Recent findings from our group may offer a clue to explain the maintained inflammatory reaction in SBP. When studying sequential samples of blood from SBP patients under antibiotic therapy, we observed the maintenance of molecular evidence of BT as demonstrated by the presence of bacterial genomic fragments in blood.