Thermal injury induces an inflammatory response that contributes to the development of secondary tissue damage. Neutrophil recruitment and activation are in part responsible for this tissue damage. Although γδ T cells have been shown to regulate the inflammatory responses in tissues that are prone to neutrophil-mediated injury post-burn, their role in the induction of secondary tissue injury post-burn remains unknown. To study this, γδ T cell-deficient (γδ TCR-/-) and wild-type (WT) mice were subjected to thermal injury or sham procedure, and tissue samples were isolated 1-24 h thereafter. Burn injury induced neutrophil accumulation in the lung and small intestines of WT mice at 1-3 h post-injury. No such increase in neutrophil tissue content was observed in γδ TCR-/- mice. An increase in tissue wet/dry weight ratios was also observed in these organs at 3 h post-burn in WT but not in γδ TCR-/- mice. A parallel increase in plasma and small intestine levels of the chemokines macrophage-inflammalory protein-1β (chemokine ligand 4) and keratinocyte-derived chemokine (CXC chemokine ligand 1) were observed in injured WT mice but not in injured γδ TCR-/- mice. Increased activation (CB120b expression) of the circulating γδ T cell population was also observed at 3 h post-burn in WT mice. These results indicate the γδ T cells, through the production of chemokines, play a central role in the initiation of neutrophil-mediated tissue damage post-burn.