ABSTRACT Objective To better characterize the genetic factors, implicated in oxidative pathway, determining susceptibility to inflammatory bowel disease (IBD), we assessed for the first time the potential role of NOS2A , HIF1A and NFKB1 polymorphisms on the risk of developing IBD in Moroccan population. Methods The distribution of (TAAA)n_rs12720460 and (CCTTT)n_rs3833912 NOS2A microsatellite repeats, HIF-1A _rs11549467 and NFKB1 –94ins/delATTG_rs28362491 was analyzed in 507 subjects grouped in 199 IBD and 308 healthy controls. Genotyping was performed with polymerase chain reaction-fluorescent method and the TaqMan® allelic discrimination technology. Results The allele and genotype frequencies of HIF1A _rs11549467, NFKB1 _rs28362491 and NOS2A _(TAAA)n did not differ significantly between patients and controls. Analysis of NOS2A _(CCTTT)n markers evidenced differences between patients and healthy controls. A preferential presence of the (CCTTT)8 (P=0.02; OR=1.71, 95%CI=1.07–2.74), (CCTTT)14 (P=0.02; OR=1.71, 95%CI=1.06–2.76) alleles in IBD, (CCTTT)8 (P=0.008; OR=1.95, 95%CI=1.17–3.23) in CD and (CCTTT)7 (P=0.009; OR = 7.61, 95%CI=1.25-46.08), (CCTTT)11 (P=0.05 ; OR= 0.51, 95%CI=0.25-1.01), (CCTTT)14 (P=0.02 ; OR= 2.05, 95%CI=1.07-3.94), (CCTTT)15 (P=0.01 ; OR= 2.25, 95%CI=1.16-4.35) repeats in UC patients indicated its possible association with higher disease risk which need to be confirmed in a larger sample size. Conclusion Our results suggest that the NOS2A _(CCTTT)n gene variations may influence IBD susceptibility in the Moroccan population.