Background: Inflammatory bowel disease (IBD) is a chronically relapsing disease. It includes ulcerative colitis (UC) and crohn's disease (CD). Symptoms of IBD could be conflicting sometimes with irritable bowel syndrome (IBS) of diarrheal type. The ideal marker for IBD/IBS diagnosis has not yet been identified. B2 microglobulin (B2-M) is a low molecular weight protein released by activated T and B lymphocytes. It has been shown to increase in several chronic inflammatory conditions. Objectives: Assessment of the diagnostic role of (B2-M) in IBS cases presented with diarrhea (IBS-D type) and UC cases. Methodology: This case control study was conducted at Gastroenterology Unit in Tropical Medicine Department, Ain- Shams University Hospitals, Cairo, Egypt. Forty patients with UC, and twenty patients with IBS in addition to twenty healthy persons as control were included. Results: There was a higher mean of B2-M values among U.C group (1.93)(mean B2-M in Active UC was 2.26 and 1.61 in inactive disease) compared to the other two groups(1.51 in IBS and 1.43 in control group) and the difference was highly statistically significant(P=0.000).Using ROC curve analysis of different cut off values of (B2-M) for detection of UC cases among IBS cases, we found that at a cut off value of <1.5 , we got sensitivity, specificity, PPV, NPV and accuracy of 75 %, 70 %, 83.3%, 58.3 %, and 0.753% respectively and this was the best cut off value. Conclusion: B2-M level may have a diagnostic and differentiating utility between UC cases and IBS-D type as well as a potential indicator of disease activation in UC patients.