Background: The amount of Serum Leucine Rich Glycoprotein (LRG) has a strong correlation with the clinical disease activity observed in patients with Crohn's disease (CD). Aim: to determine the Leucine rich glycoprotein serum level in patients with CD. Patients and Methods: This prospective cohort study was carried out at Internal Medicine and Clinical Pathology Departments, Zagazig University Hospitals on 16 patients complaining of CD. The following were done for all patients: detailed history, complete general examination, local abdominal examination, examination of other systems and upper endoscopy findings with biopsy. Colonoscopy was done if there was no contraindication. Colonoscopy was done by two senior experts and by OLYMPUS colonoscope. Fecal calprotectin was measured and serum LRG was quantified using ELISA kit at the baseline and after 6 months as the patients had their biological treatment and subjected to follow up for six months. Results: Activity of CD had a significant relation with Harvey Bradshaw score (p=0.005). On pairwise comparison, difference was significant between remission and each of newly diagnosed and relapse (p=0.034, and 0.002 respectively). Severity of CD had a significant relation with Harvey-Bradshaw score (p<0.001). On pairwise comparison, difference was significant between remission and moderate CD (p<0.001). The best cutoff of baseline LRG in diagnosis of Crohn’s disease in remission is ≤61.4 µg/ml with area under curve 0.855 with sensitivity 80%, specificity 81.8%, positive predictive value 66.7%, negative predictive value 90% and overall accuracy 81.3% (p=0.027). There is statistically significant positive correlation between baseline LRG and Harvey-Bradshaw score, CRP and serum creatinine. There is significant decrease in LRG in remission and mild cases after treatment. Conclusion: Leucine-rich glycoprotein could be a reliable serum biomarker for the assessment of clinical disease activity in patients with IBD. It can be an alternative to CRP and fecal calprotectin for the assessment of Crohn's disease.