Ulcerative colitis is an autoimmune-inflammatory disease characterized by increased proliferation of colonic epithelial cells, dysregulation of signal transduction pathways, elevated mucosal T-cell activation, increased production of pro-inflammatory cytokines, and enhanced leukocyte infiltration into colonic interstitium. Several compounds that possess anti-proliferative properties and/or inhibit cytokine production exhibit a therapeutic effect in murine models of colitis. Mammalian target of rapamycin (mTOR), a protein kinase regulating cell proliferation, is implicated in colon carcinogenesis. In this study, we report that a novel haloacyl aminopyridine based molecule (P2281) is a mTOR inhibitor and is efficacious in a murine model of human colitis. In vitro studies using western blot analysis and cell-based ELISA assays showed that P2281 inhibits mTOR activity in colon cancer cells. In vitro and in vivo assays of pro-inflammatory cytokine production revealed that P2281 diminishes induced IFN- production but not TNF- production indicating preferential inhibitory effects of P2281 on T-cell function. In the DSS model of colitis (i) macroscopic colon observations demonstrated that P2281 significantly inhibited DSS-induced weight loss, improved rectal bleeding index, decreased disease activity index and reversed DSS-induced shortening of the colon; (ii) histological analyses of colonic tissues revealed that P2281 distinctly attenuated DSS-induced edema, prominently diminished the leukocyte infiltration in the colonic mucosa and resulted in protection against DSS-induced crypt damage and (iii) western blot analysis showed that P2281 blocks DSS-induced activation of mTOR. Collectively, these results provide direct evidence that P2281, a novel mTOR inhibitor, suppresses DSS-induced colitis by inhibiting T-cell function, and is a potential therapeutic for colitis. Given that compounds with anti-cancer activity show promising anti-inflammatory efficacy, our findings reinforce the cross-therapeutic functionality of potential drugs.