Background and aim <p>Despite advances in understanding inflammatory bowel disease (IBD)’s etiology, its precise molecular mechanisms remain poorly understood, limiting the efficacy of existing therapies. Recently, long non-coding RNAs (lncRNAs) have emerged as crucial regulatory molecules influencing immune responses and inflammatory pathways in IBD. This study aimed to assess the expression levels of lncRNA TDRG1 and ETV4 mRNA as potential markers for distinguishing ulcerative colitis (UC) from Crohn’s disease (CD) and assessing disease activity.</p> Methods <p>This case control study included 120 participants, divided into three groups: 40 patients with UC, 40 with CD, and 40 healthy controls. Patients were then divided into active and inactive subgroups, based on clinical, laboratory and endoscopic parameters. Plasma expression levels of lncRNA TDRG1 and ETV4 mRNA were quantified using real time qPCR.</p> Results <p>Plasma levels of the lncRNAs TDRG1 and ETV4 mRNA were significantly higher in the UC and CD groups than in the healthy controls, and in UC patients compared to CD patients. Moreover, active CD patients showed significantly higher values than inactive group, while the expression levels in active UC patients were higher than inactive group but not statistically significant.</p> Conclusion <p>This study revealed that plasma lncRNA TDRG1 and ETV4 mRNA are valuable indicators of IBD and can help distinguish UC from CD. Their strong association with CD activity suggests potential utility as biomarkers for early detection of disease activity, guiding timely management and potentially improving patient outcomes.</p>