The Thalassophryne nattereri fish venom induces a severe burning pain, oedema, and necrosis observed both clinically and experimentally. The present study was carried out in order to describe the pattern of local acute inflammatory response after T. nattereri venom injection. Our findings show that the edematogenic response induced by T. nattereri venom in footpad of mice was dose- and time dependent, and remained significantly elevated over 48 h after injection. Analysis of footpad homogenates were tested for the presence of TNF-alpha, IL-1beta and IL-6, and demonstrated augmented levels of these cytokines. Our results showed that the injection of venom developed an inadequate cellular inflammatory response evidenced by poor infiltration of mononuclear cells, preceded by decreased number of these cells in peripheral blood. In contrast, we observed an early intense recruitment of neutrophil to peritoneal cavity, accompanied by a significant decrease in the number of mononuclear cells. A drastic increase in the total amount of cells, mainly in neutrophils, followed by mononuclear cell recruitment was observed 24 h. In addition, we also demonstrated that T. nattereri venom affects the viability of mononuclear cells (J774A1) in culture. We conclude that the scarcity of inflammatory cellular influx into local lesions (intraplantar) induced by T. nattereri venom could be a consequence of an impaired blood flow in venules at injured tissue and cytotoxic effect of the venom on inflammatory cells can contribute to this impairment.