Vasoactive intestinal peptide (VIP) is a 28aa peptide (human, chr 6q26-q27). Expressed and secreted by neurons innervating primary and secondary immune organs such as lymph nodes. VIP is a potent neurotrophic factor causes vasodilation, lowers arterial blood pressure, and relaxes the smooth muscle of trachea, stomach and gall bladder. VIP also modulates several T-lymphocyte activities including motility, cytokine production, proliferation and apoptosis, VIP exerts its biological activity by binding to two closely related class II G-protein-coupled receptors VPAC-1 and VPAC-2 beside this VIP has its own receptors VIPR1&2 (Vasoactive Intestinal Polypeptide Receptor 1&2) and VIPRRP (VIP receptor-gene repressor protein). VIP shows similarities to glucagon, secretin and gastric inhibitory peptide (GIP) as such it has been considered a member of the glucagon-secretin family. The VIP is 100% conserved in mouse, rat and human. VIP is considered to be a viable candidate for the development of treatments for rheumatoid arthritis, since treatment with VIP significantly reduced incidence of severity of arthritis, the therapeutic effect of VIP was associated with downregulation of both inflammatory and autoimmune components of the disease.