Transferrins belong to a family of iron-binding proteins that have been implicated in innate immunity and in vitellogenesis in insects. Here we have sequenced and characterized a full-length cDNA encoding a putative iron-binding transferrin (AmTRF) in the honeybee. AmTRF shows high level of sequence identity with transferrins in both vertebrates and insects (26–46%) suggesting that the primary function of the predicted 712 amino acid protein is binding and transporting of iron. AmTRF is expressed ubiquitously, but particularly high levels of its mRNA are found in the central brain and in the compound eye. Using northern blotting and a microarray based approach we have examined the levels of AmTRF mRNA by expression profiling under a wide range of conditions including developmental stages, septic injury and juvenile hormone treatment. Increased expression of AmTRF is seen during early pupal stages, in the brain of mature foragers and in the abdomen of virgin queens, whereas treatment with juvenile hormone leads to a decrease of AmTRF levels in the abdomen. We show that a transcriptional response of transferrin to septic injury with E. coli is relatively moderate as compared to a dramatic up-regulation of an antibacterial polypeptide, Hymenoptaecin, under similar conditions. We conclude that major fluctuations of AmTRF mRNA in time and space are consistent with context-dependent functional significance and suggest broader multifunctional roles for transferrin in insects.