Background: Inflammatory bowel disease (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder, characterised by relapsing and remitting course. As a pattern recognition receptor, RAGE has a known role in intestinal inflammatory responses via the activation of multiple intracellular signalling molecules, such as NF-κB, and mediates neutrophil migration across intestinal epithelial in inflamed intestinal lumen. Aim: We aimed to study the association between RAGE promoter gene polymorphisms (-374T>A & -429 T>C) and risk of disease development, and probable effect on clinical characteristics and management. The study was conducted on 81 control subjects and 90 IBD patients (71 UC & 19 CD), genotyping of -374T>A & -429 T>C SNPs was done using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-REFLP). Results: when CD genotypes compared with UC genotypes, the genotype AA and A allele were significantly associated with CD (P=0.014 & 0.026). No significant association between CD and -429T/C genotype, however, the genotype TC of -429T>C SNP might decrease the risk of UC disease (P=0.049, OR=0.047,CI(0.22-0.98)), in addition, patients with extra intestinal manifestations and carrying C allele (TC or CC) were more than those carrying the TT genotype (P=0.007, OR= 22.08, CI= 3.19-444.38) and also patients receiving to biological treatment were having C allele more than TT genotype (P= 0.023, OR=3.9, CI=1.21-12.95). Conclusion: These observed results suggest that RAGE may have a role in disease development and may influence the disease phenotype and further may affect the choice of medical treatment.