Inflammatory bowel disease (IBD) refers to a group of heterogeneous disorders associated with chronic inflammation of the gut, having a high rate of incidence in the world. In the present review, we will discuss the link between the short-chain fatty acids, especially butyrate (BT), produced by bacterial fermentation of dietary fiber, and IBD development. Current knowledge supports an anti-inflammatory role for BT and suggests that BT insufficiency may be involved in the pathogenesis of IBD. We will present the molecular mechanisms involved in the anti-inflammatory effect of BT, namely histone deacetylase inhibitor activity, activation of PPARγ and of GPR109A, GPR41 and GPR43 receptors. The histone deacetylase inhibitor activity of BT depends of its absorption by colonocytes. Therefore, BT transporters are also important players in BT-induced anti-inflammatory effect at colonic level. Finally, BT-based future prospects for IBD therapy (modulation of diet (through increased prebiotic (fiber) ingestion) and microbiota (BT-producing probiotic bacteria) supplementation - that can increase the levels of BT in colon - and development of pharmacological BT analogues) will be presented.