Background: Crohn's disease (CD) and ulcerative colitis (UC) are examples of inflammatory bowel diseases (IBDs), which are chronic gastrointestinal tract illnesses with no known cause. In UC, there is a correlation between leucine-rich alpha-2 glycoprotein (LRG) and clinical disease activity. The purpose of this study was to evaluate the relationship between UC patients' LRG serum levels and their illness activity and severity. Method: We performed this prospective cohort study on 36 Ulcerative colitis patients. C-Reactive Protein (CRP), serum urea, creatinine, total bilirubin and fecal calprotectin were assessed. Serum LRG levels were measured by using double antibody sandwich enzyme-linked immunosorbent assay (ELISA). Results: The best cutoff of baseline LRG for diagnosing severe UC in comparison to mild and moderate cases was ≤67.4µg/ml with area under curve 0.913 with sensitivity 91.7%, specificity 87.5%, positive predictive value 78.6%, negative predictive value 95.5% and overall accuracy 91.7% (p=0.002). A statistically significant positive correlation was revealed between baseline LRG and Mayo score (p<0.001). A significant difference was found between mild, moderate & severe disease groups with baseline LRG (p<0.001). On comparing each two groups with one way ANOVA and Mann Whitney test, the difference was significant between mild and both moderate and severe disease (significantly lower in mild group with p values of 0.013, and <0.001 respectively). 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 ulcerative colitis disease.