Venom is a complex mixture of many substances such as toxins, enzymes, growth factor activators, and inhibitors are particularly responsible for the deleterious effects of cells. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Envenomation by bees, scorpions, snakes, spiders and wasps involves the activation of the inflammatory response with the release and activation of pro-inflammatory cytokines and other mediators, such as nitric oxide. Recently, a battery of cytokines produced by activated T cells or macrophages have been added to in envenomations. Cytokines are important for the interactions between cells in the immune and inflammatory responses. Although the pathophysiology of envenomation is not fully understood, venom and immune responses are known to trigger the release of cytokines and nitric oxide. The cytokines initiate a cascade of events that lead to illness behaviors such as fever, anorexia, and, as well as a host of physiologic events such as activation of vasodilation, hypotension and increased nitric oxide production. Accumulating evidence indicates that these cytokines play important roles in mediating cell recruitment and activation necessary for inflammation and the repair of tissue damage. A better understanding of the involvement of the inflammatory system in different envenoming syndromes may have future therapeutic benefits.