Recent studies on the molecular pathogenesis of Salmonella enterica serotype Typhimurium-induced enterocolitis using tissue culture models and the neonatal calf model have led to an improved understanding of key events occurring during the complex series of host-pathogen interactions leading to diarrhea. In vitro studies show that Salmonella serovar Typhimurium translocates a number of type III secreted effector proteins, including SipA, SopA, SopB, SopD, and SopE2 into host cells. SipA, SopA, SopB, SopD, and SopE2 are required for eliciting infiltration of neutrophils in the calf model of enterocolitis, presumably by inducing the production of chemoattractant chemokines in bovine ileal tissue during Salmonella serovar Typhimurium infection. The resulting acute inflammatory response is associated with an increase in vascular permeability resulting in mucosal edema. Furthermore, the influx of neutrophils is associated with necrosis of the uppermost ileal mucosa. The injury to the intestinal epithelium leads to leakage of extravascular fluids and massive transmigration of neutrophils into the intestinal lumen, a process normally prevented by the epithelial permeability barrier. These data suggest that the severe fluid loss observed during Salmonella serovar Typhimurium-induced enterocolitis is at least in part due to an inflammatory mechanism which causes liquid to flow from the blood to the intestinal lumen.