Pharmacological levels of zinc oxide in the post-weaning piglet diet reduce the incidence and severity of diarrhoea, in particular that caused by enterotoxigenic Escherichia coli (ETEC) K88 (Owusu-Asiedu et al. 2003). A previous in vivo genomic study (Sargeant et al, 2008) identified several genes differentially expressed in the small intestine of ETEC-challenged piglets when fed a zinc oxide-supplemented diet. This included decreased expression of several genes involved in the inflammatory and innate immune response. It has been reported that ZnO reduces adhesion and internalisation of K88 to cultured human enterocytes, counteracting the up-regulation of inflammatory cytokines caused by ETEC infection. However, this effect was not due to growth inhibition of ETEC K88 in ZnO (Roselli et al, 2003). The objective of this study was to determine whether zinc oxide shows the same mode of action in protecting porcine intestinal cells against ETEC K88 as has been demonstrated in human cells, providing an explanation for in vivo findings.