The intestine is a highly vascularized organ, and the splanchnic microcirculation is now appreciated to play a key role in immune and inflammatory responses in the gut. Emerging evidence demonstrates that the enteric flora not only exerts an important effect on innate immunity and the mucosal immune system, but will also affect inflammatory and angiogenic mechanisms involving the gut microcirculation. In response to bacterial lipopolysaccharide, the intestinal microcirculation and its endothelial lining will undergo activation, which will contribute to cell adhesion molecule expression and the recruitment of leukocytes into the gut wall, an early and rate limiting step in the inflammatory process. This is balanced by the fact that human intestinal microvascular endothelial cells possess specific mechanisms of endotoxin tolerance, which will diminish inflammatory activation in response to repeated bacterial activation. Likewise, the process of angiogenesis, or new blood vessel growth is influenced by the presence of bacteria, which stimulate the release of angiogenic factors from innate immune mechanisms. Conversely, bacterial derived products of dietary carbohydrate fermentation, the short chain fatty acids, will decrease angiogenic mechanisms in human intestinal microvascular endothelial cells. In this review we summarize our present state of knowledge regarding the interplay between enteric flora and inflammatory and angiogenic activation of the intestinal microcirculation its microvascular endothelium.