Salmonella enterica serovar typhimurium (S. typhimurium) species are a leading cause of human invasive gastroenteritis. There is increasing in vitro evidence about Salmonella interaction with isolated cells or cell lines (macrophages, and enterocytes) on the molecular level, however, very little is known about in vivo interactions during actual invasion. We investigated the early interaction of S. typhimurium with intact small intestinal mucosa, in a pig model. Intestinal segments were infected with or without S. typhimurium DT104, and perfused. Whole mucosal gene expression was analyzed by cDNA array on 0, 2, 4, and 8h post-infection. Invasion resulted in the upregulation of only eight transcripts in jejunal mucosa, among those the proinflammatory IL-8 (at 4h only), and the antiinflammatory STAT3 (at 4 and 8h). The limited number of differentially expressed genes found here in vivo compared to in vitro is most likely due to the presence of multiple, heterogenous cell interactions in intact mucosa. Furthermore, it is concluded that S. typhimurium evades strong host responses by downregulating the local inflammatory response.