We sought to correlate the characteristic changes in goblet cell morphology in the chronically inflamed large intestine of 1L10-/- mice to specific changes in goblet cell gene expression. In healthy as well as IL10-/- mice, marked differences were found among the large intestinal regions in goblet cell morphology and gene expression. The mucin Muc2, which is a major determinant of goblet cell morphology, was expressed in most goblet cells, yet only in cells staining positive for both Alcian blue and high iron diamine. TFF3 was expressed in only a small subset of goblet cells. Inflamed colon of IL10-/- mice still contained high numbers of small, hypotrophic goblet cells with similar histochemical staining and Muc2 and TFF3 expression patterns, contradicting the often reported "goblet cell depletion" in colitis. Quantitatively, the Muc2 and TFF3 levels remained relatively stabile in IL10-/- mice. Muc2 in distal IL10-/- colon contained significantly less sulfate residues than in controls, which may compromise its protective properties.