Many of the anabolic effects of growth hormone (GH) act through insulin-like growth factor-I (IGF-I). Systemic administration of GH in combination with IGF-I has been shown to stimulate wound reepithelialization, however, it causes hyperglycemia or hypoglycemia, respectively. We hypothesize that very low doses of IGF-I in a liposome form will have the same positive wound-healing effect when administered locally as the higher doses of GH plus IGF-I given systemically. To test this hypothesis, rats were given a 40% TBSA full-thickness scald injury and received either placebo IGF-I (5.0 mg/kg/day, subcutaneously), IGF-I liposome (0.9 microgram/kg/week, subcutaneously), or a combination of GH and IGF-I, or IGF-I liposomes for 8 weeks. GH in combination with IGF-I showed a significant increase in postburn weight. Wound reepithelialization, measured by computerized planimetry as percentage original wound area, was significantly increased in rats receiving GH plus IGF-I, GH plus IGF-I liposomes, and IGF-I liposomes when compared to sham, or IGF-I (p < 0.05). Results indicate that small doses of IGF-I, delivered in the form of liposomes, are equally effective in increasing burn wound reepithelialization as the higher doses of GH plus IGF-I, or GH plus IGF-I liposomes.