BACKGROUND: New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUD(HP-beta-CD)) and poloxamers (PL) were developed for future clinical use. AIMS: This study evaluated the efficacy of such novel formulations in a rat model of colitis. METHODS: The PL-BUD(HP-beta-CD) systems were prepared by direct dispersion of the complex (BUD concentration 0.5 mg mL(-1)) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5 days by a rectal route, as follows: BUD 1: BUD(HP-beta-CD) + PL407 (18%); BUD 2: BUD(HP-beta-CD) + PL407 (20%); BUD 3: BUD(HP-beta-CD) + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUD(HP-beta-CD); C1: HP-beta-CD + PL407 (18%); C2: HP-beta-CD + PL407 (20%); C3: HP-beta-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-alpha, IL-1beta, IL-10 and endogenous glucocorticoids were obtained using ELISA. RESULTS: BUD(HP-beta-CD) poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUD(HP-beta-CD) and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUD(HP-beta-CD) (p < 0.01). All formulations with BUD(HP-beta-CD) poloxamers reduced TNF-alpha levels (p < 0.05). CONCLUSION: Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-alpha levels.