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Introduction: Proteins are absorbed primarily as short peptides via peptide transporter 1 (PepT1).Hypothesis: Intestinal adaptation for peptide absorption after massive mid-small intestinal resection occurs by increased expression of PepT1 in the remnant small intestine and colon.Methods: Peptide uptake was measured in duodenum, jejunum, ileum, and colon using glycyl-sarcosine 1 week (n = 9) and 4 weeks (n = 11) after 70% mid-small bowel resection and in corresponding segments from unoperated rats (n = 12) and after transection and reanastomosis of jejunum and ileum (n = 8). Expression of PepT1 (mRNA, protein) and villus height were measured.Results: Intestinal transection/reanastomosis did not alter gene expression. Compared to non-operated controls, 70% mid-small bowel resection increased jejunal peptide uptake (p < 0.05) associated with increased villus height (1.13 vs 1.77 and 1.50 mm, respectively, p < 0.01). In ileum although villus height increased at 1 and 4 weeks (1.03 vs 1.21 and 1.35 mm, respectively; p < 0.01), peptide uptake was not altered. PepT1 mRNA and protein were decreased at 1 week, and PepT1 protein continued low at 4 weeks. Gene expression, peptide uptake, and histomorphology were unchanged in the colon.Conclusions: Jejunal adaptation for peptide absorption occurs by hyperplasia. Distal ileum and colon do not have a substantive role in adaptation for peptide absorption. [ABSTRACT FROM AUTHOR]