PCR‐based subtractive hybridization was used to isolate genes preferentially expressed in a termite (Mastotermes darwiniensis) following exposure to an entomopathogenic fungus. The subtraction procedure yielded a cDNA clone encoding a putative transferrin that, when sequenced to its ends, is the largest (728 amino acids) for any insect transferrin characterized to date. Cysteines and residues comprising putative iron‐binding sites are conserved in both N‐ and C‐terminal lobes, suggesting structural and functional similarity to diferric vertebrate transferrins. A quantitative PCR assay confirmed a significant increase in transferrin expression following infection, suggesting its up‐regulation is part of the innate immune response. However, codon‐based tests for selection among known insect transferrins revealed only a small proportion of codon‐sites positively selected. Thus, unlike certain vertebrate transferrin lineages, no widespread evidence for pathogen‐mediated positive selection was detected at this locus.