Dietary supplementation with animal plasma proteins can prevent intestinal inflammation induced by enterotoxin B of S. aureus in rats, and reduce the lung inflammatory response induced by LPS in mice. The mechanism of action involves the modulation of the gut associated and nasal associated lymphoid tissue, respectively. We have also shown that dietary supplementation with plasma proteins can reduce the structural and functional changes observed in the colon during the development of spontaneous colitis. This study examined the effects of these supplements on the expression of mucosal mucins and of a representative tight-junction protein, as they are determinant for the permeability properties of the crypt epitheilium. Wild-type (WT) mice and mice lacking mdr1a gene (KO) were obtained from Taconic (Germantown, NY) and maintained in the Animal Facility Service of the Barcelona Science Park (n = 10-12 mice per group). Mice were grown and maintained in specific pathogen free conditions until week 4 when they were transferred to conventional housing. Animals were supplemented with spray-dried porcine plasma protein (SDP, 8% w / w) or milk proteins (control diet). Diets were fed from day 19 (weaning) until day 56. The index of disease activity (DAI) was recorded throughout the experimental period. The permeability of the mucosa of the colon was analysed ex vivo by confocal microscopy using FITC-dextran 10 kDa as marker; the expression of E-cadherin was measured by Western blot, and the expression of transmembrane mucines MUC1 and MUC4 and secretory mucin MUC2 by RT-PCR. DAI increased progressively from day 39, reaching a value of 2.8 ± 0.5 in KO mice (0.7 ± 0.3 in WT controls, P <0.05) at 56 days and this correlated well with the Histopathological index and the goblet cell depletion index. MUC1 expression was increased 4 times and no effects of diet were observed; MUC4 expression was increased 3-fold and this effect was prevented in part by SDP. The expression of secretory MUC2 followed the profile of goblet cell depletion, as expected. SDP was also effective in reducing the changes in MUC4 and MUC2 observed during colitis consolidation. Increased mucosal permeability in the KO mice was inversely correlated with E-cadherin expression. Both effects were prevented by dietary SDP. We conclude that dietary supplementation with SDP is able to prevent in part the changes in the expression of transmembrane and secretory mucines, and of junctional E-cadherin during the development of spontaneous colitis. The good correlation between DAI and crypt permeability indicates that junctional proteins and mucine production are adequate markers of the colitis syndrome.