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Background/purpose: Glucagonlike peptide-2alpha (GLP-2alpha) has been shown to be a growth factor for the small intestine. This study investigated the benefits of intravenous and intraluminal administration of GLP-2alpha using a rat model of inflammatory bowel disease (IBD)., Methods: Normal Fisher rats and HLA-B27 (IBD) rats were treated for 14 days as follows: Fisher, intravenous saline (n = 6); HLA-B27, intravenous saline (n = 6); HLA-B27, intravenous GLP-2alpha (50 microg/kg/d; n = 5); Fisher, intraluminal saline (n = 5); HLA-B27, intraluminal saline (n = 5); or intraluminal GLP-2alpha (50 microg/kg/d; n = 5). Rats were evaluated for frequency of diarrhea, and the bowel was analyzed for gross and microscopic lesions. Statistical evaluations were determined using analysis of variance (ANOVA). A P value of.05 was significant., Results: Intravenous GLP-2alpha decreased diarrhea and the number of bowel lesions (P <.05). Microscopic inflammation was reduced by 24% but was not statistically significant. Intraluminal GLP-2alpha decreased the number of small intestine lesions (P <.05) and the microscopic inflammation (P <.05) but did not significantly reduce diarrhea or the overall number of bowel lesions., Conclusions: GLP-2alpha ameliorates the signs of IBD in HLA-B27 rats. Intravenous GLP-2alpha reduces diarrhea more effectively than intraluminal administration, and both routes are equally effective in ameliorating inflammation. GLP-2alpha potentially provides a new modality for the treatment of IBD.