The entomopathogenic fungus Metarhizium anisopliae is a candidate for biological control of subterranean termites and its virulence has been shown in some laboratory studies. However a successful field trial has yet to be reported. Disease resistance mechanisms are still not fully understood as few studies have focused on the specific cellular interaction between this pathogen and subterranean termites. This study provides evidence of a cellular response by Reticulitermes flavipes to M. anisopliae invasion through the integument, suggesting that subterranean termites have evolved complex immune mechanisms against soil fungal pathogens.