Crohn’s Disease (CD) is an inflammatory bowel disease, in which there is the inflammation extension in the whole thickness of the intestinal wall. The CD occurrence is rising globally among the youth [6], Endoscopy has a key function in evaluating mucosal lesions. But it is expensive and has complications. So far, there are no optimal biomarkers available to detect and monitor CD. The aim of this study is to explore the role of Lipocalin 2 and Nitric Oxide Synthase 2 Gene Expression as indicators for the CD diagnosis. A total of 81 Egyptian subjects were enrolled in the study. The levels of Lipocalin 2 and Nitric Oxide Synthase 2 Gene Expression were assessed in mucosa samples from 27 healthy controls (group I), 27 CD patients (group IIA), and 27 CD patients with complications (group IIb) by quantitative real time –PCR (qRT-PCR). Significant increase of Lipocalin 2 and Nitric Oxide Synthase 2 Gene Expression values in group IIA and group IIB than group I. Both miR 16 and miR 106a showed a positive correlation with ESR and CRP. ROC curves of lipocalin 2 for CD detection had a sensitivity of 92.6% and a specificity of 88.9%. ROC curves of miR nitric oxide synthase 2 diagnosis CD demonstrated 96.3% sensitivity and 88.9% specificity. Levels of lipocalin 2 and nitric oxide 2 may serve as valuable diagnostic and prognostic indicators for this CD.