BACKGROUND/AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease affecting the colon. Mesenchymal stem cells (MSCs) are candidates for use in inflammatory diseases with their tissue regeneration and anti-inflammatory capabilities. Chemokine receptor overexpression on MSCs is an effective strategy for the migration of MSCs into inflammatory tissue in high amounts. In this study, the anti-inflammatory and regenerative effects of genetically CCR2 overexpressed gingiva MSCs (GMSCs) on the inflamed colon in UC were studied. MATERIALS AND METHODS: GMSCs were transduced with a lentiviral vector for CCR2 overexpression. The UC experimental model was induced with a single intrarectal administration of 4% w/w acetic acid. Colon tissues were analyzed for IFN or IL-17 secreting CD4+ T lymphocytes via flow cytometry and lymphocytic infiltration, fibrosis, and ulcers by histopathologic evaluation. Homing analysis of GMSCs was done by analyzing fluorescence intensity under the fluorescence microscope. RESULTS: GMSCs and CCR2+GMSCs equally downregulated colonic IFN-gamma or IL-17 secreting CD4+ T lymphocytes ratios compared to the untreated group (p < 0.05). Fluorescence intensity of labeled cells was significantly high in colon tissues of CCR2+GMSCs administered rats (61.2 +/- 13.7%) compared to GMSCs administered rats (19.6 +/- 9.8%) (p < 0.05). In addition, mucosal integrity significantly increased and fibrosis and ulcers notably decreased in CCR2+GMSCs administered rats compared to GMSCs administered rats (p < 0.05). CONCLUSION: The overexpression of CCR2 on GMSCs increases migration to the inflammatory colon tissue, which has a high regenerative effect in UC. Overexpression of CCR2 on GMSCs may be an alternative to cellular therapies in UC.