Background: Inflammatory bowel disease (IBD) involves mainly Crohn's disease (CD) and ulcerative colitis (UC). Distinguishing between the two dise-ases may be problematic in 15% of patients due to inconclusive findings on histopathology or endos-copy. miRNAs are non-coding RNAs composed of 18-23 nucleotides and are widely detected in the cells involved in variable pathological and physiological processes. The aim of this study is to assess if serum microRNA 106 and microRNA 223 (miR-223) can be reliable biomarkers in IBD patients. Methods: Serum levels of microRNA 106 and microRNA 223 (miR-223) were determined in 80 IBD patients by using the Transcript or First Stand cDNA, expression levels of serum miRNA in IBD patients and the control group and between active and inactive diseases were detected. Results: There was a significant increase in expression levels of serum miRNA 106 and miRNA 223 in IBD patients (UC and CD) compared to the control group (P<0.001, both). Also, There was a significant incr-ease of expression levels of serum miRNA 106 and serum miRNA 223 with increased disease activity of IBD (P <0.05, both). Conclusions: The levels of miRNA 106 and miRNA 223 are higher in the peripheral blood of IBD patients and the elevation is more significant in the active disease. The miRNA 106 and miRNA 223 may be used as a novel biomarker in the diagnosis of IBD and evaluating the disease activity.