In previous studies we have shown that dietary supplementation with spray-dried porcine plasma proteins (SDP) attenuates the effects of the S. aureus enterotoxin B (SEB) on activation of gut-associated lymphoid tissue (GALT) and increased intestinal permeability. We have now studied if the effects of plasma supplementation correlated with mucosal cytokine release and defensin expression. Wistar–Lewis rats were fed diets supplemented with SDP (8% w/w), with a plasma protein fraction containing 50% Ig (PPF; 1.5% w/w) or with milk proteins (Control diet), Animals were fed experimental diets from weaning (day 21) until day 35 after birth, and on days 32 and 35, were administered SEB (i.p. 0.5 mg/kg) to induce a mild intestinal inflammation. Experimental groups were Control, SEB, SEB-SDP and SEB-PPF. Cytokines were determined by a cytometric bead array assay, LTB 4 by ELISA and iNOS and defensins by real time PCR, all at 6 h after SEB administration. Results showed that SEB significantly increased mucosal IFN-γ, TNF-α, IL-6 and LTB 4 concentration (by 110%, 20%, 30% and 110%, respectively; all P < 0.05). SDP and PPF partially attenuated these effects. SEB increased mucosal iNOS expression by 22% (P < 0.05) and both plasma protein supplements prevented SEB effects on iNOS expression (both P < 0.05). SEB administration also reduced the expression of β-defensin 1 and cryptdin 4 about 10% (P < 0.05) and both supplements significantly prevented these effects (P < 0.05). SDP increased the expression of mucosal IL-10 supporting the view that this anti-inflammatory cytokine participates in the mechanism of action of dietary plasma proteins during intestinal inflammation.