Major thermal injury results in severe prolonged responses with three components: a hypermetabolic response, inflammatory responses and endogenous wound healing processes. We have previously shown that use of liposomal-mediated gene transfer of the insulin-like growth factor I (IGF-I) reduces burn-induced inflammatory responses and enhance wound healing. In the present study, we found transient increased levels of IGF-I protein in rats exposed to thermal trauma via liposomal gene transfer in an effort to define the transcriptional events that occur following IGF-I delivery at the site of injury. The beneficial effects of IGF-I gene transfer act partly via amelioration of burn-induced inflammatory responses that mediate cell death through caspase-3 activity and Bax expression. IGF-I gene transfer induces selective stimulation of AP-1 DNA binding activity and the activation of anti-apoptotic but not the inflammatory NF-B transcription factors. Data were consistent with our hypothesis that the beneficial effects of IGF-I gene transfer on burned rats act in part via AP-1 and NF-B transcriptional regulation and the concordance between the results obtained with anti-apoptotic as opposed to the pro-apoptotic sequences as well as the corresponding changes in measures of cell death via Bax and caspase-3 mechanisms.