After tail loss in lizards no infections occur indicating the presence of an effective anti-microbial barrier in the exposed tissues of the tail stump. Previous molecular studies on the lizard Anolis carolinensis have identified some beta-defensin-like genes and the deduced peptides that may be involved in anti-infective protection. The present study has analyzed the tissues of wounded and normal tails in lizards in order to immune-localize one of the beta-defensins previously found (AcBD15) and to detect variation in its gene expression during wounding. No immunoreactivity for this beta-defensin is present in normal tissues or in the epidermis of lizards, except for some sparse granulocytes. The latter are seen during the first 1–6 days after tail amputation and AcBD15 immunoreactivity is present in their granules. Degenerating granulocytes are incorporated, together with dead erythrocytes, platelets and keratinocytes into the scab. Real time RT-PCR and western blotting analysis indicates up-regulation of AcBD15 expression during wounding with respect to normal tissues, indicating that production, storage and release of this beta-defensin from granulocytes are active following wounding. The production of beta-defensins from granulocytes would allow protection of exposed tissues from microbial invasion avoiding a persistent inflammation, a process that leads to tissue regeneration.