Lucilia sericata maggots are used world-wide in biosurgery for the medical treatment of nonhealing wounds because they ingest necrotic tissues and significantly promote healing. To gain further insight into interdependencies between ecological adaptation and molecular evolution of innate immunity in Diptera, we used the suppression subtractive hybridization method to screen for genes that are differentially expressed in response to septic wounding of sterile second instar larvae of L. sericata. This approach resulted in the identification of 65 novel Lucilia genes including potential signalling proteins (e.g. inhibitor of apoptosis 2 protein) and a number of digestive enzymes including lipases and proteinases. Additionally, we found numerous putative antimicrobial peptides (AMPs), such as a potential Lucilia defensin, diptericin and three novel proline-rich AMPs. The identified genes may facilitate access to both peptides and proteins within the beneficial excretions, secretions and haemolymph of medicinal maggots and provide novel insights into the evolution of innate immunity in Diptera.