Intestinal inflammation is associated with various pathological diseases, such as gastritis from Helicobacter pylori infection, Crohn's and colitis in inflammatory bowel disease, and colorectal cancer. Thus, treatment with anti-inflammatory substances in these inflammation-associated diseases is critical. Increasingly compelling evidence indicates that glutamine is an anti-inflammatory compound candidate because it can influence the long-term outcome of the inflammatory diseases with in a low-risk way. However, before recommending its use in clinical practice, it is important to elucidate the molecular mechanism by which glutamine exerts its roles in modulating intestinal inflammation. In this study, we review the current knowledge on the detailed regulation pathway used by glutamine in its proinflammatory regulation, with a special emphasis on intestinal inflammation. These regulation pathways include nuclear factor kappa B (NF-κB), signal transducer and activator of transcription (STAT), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt), activating protein-1 (AP-1), nitric oxide synthases (NOS)-nitric oxide (NO), peroxisome proliferator-activated receptor-Γ (PPARγ), heat shock factor-1 (HSF-1)- heat shock proteins (HSP) and glutathione (GSH) - reactive oxygen species (ROS). Although some regulatory pathways, such as PI3K/PI3K-Akt, GSH-ROS and AP-1, need to be further investigated, this review provides useful information to utilize glutamine as an immunonutritional or pharmaconutritional drug, not only for inflammation-associated diseases in the intestine, but also possibly for other inflammatory-associated diseases, i.e. arthritis, asthma, type 2 diabetes, etc.