Helicobacter pylori is a gram-negative, bacterium that infects 50% of the world's human population. During infection, the host elicits a vigorous immune response that is insufficient to clear infection. H. pylori-mediated apoptosis of macrophages could be a possible mechanism of immune evasion. However, the bacterial factors which trigger apoptosis remain unclear. Therefore, we determined the role of cagE during H. pylori-mediated apoptosis of macrophages. Following infection with the cagE- mutant, an increase in macrophage apoptosis was detected, compared with cells infected with the wildtype (wt) H. pylori strain or uninfected controls. An increase in ERK1/2 MAPK phosphorylation was detected in cagE--infected macrophages. In addition, incubation of wt or cagE--infected macrophages with a pharmacological inhibitor, which prevents ERK1/2 phosphorylation, reduced apoptosis. These results indicate that cagE exerts anti-apoptotic effects during the infection of macrophages through the modulation of ERK1/2 MAPK.