BACKGROUND Despite its well-recognized benefits in the management of several solid tumors, the use of radiotherapy prior to surgery is associated with a high incidence of significant surgical wound healing complications. Radiation-induced damage to dermal fibroblasts has been proposed as an important cause. We hypothesized that the introduction of normal, unirradiated fibroblasts into previously irradiated skin would enhance healing of the subsequent surgical wound. METHODS Four groups of wounds were examined in female Wistar rats: (1) unirradiated skin (n = 10), (2) irradiated skin injected with tissue culture medium alone (n = 17), (3) irradiated skin injected with autologous dermal fibroblasts (n = 17), and (4) irradiated skin injected with irradiated autologous dermal fibroblasts (n = 7). Wounds were evaluated biomechanically and histologically. RESULTS The biomechanical values of breaking load, ultimate tensile strength, elastic modulus, and toughness were significantly greater in the irradiated wounds injected with fibroblasts than those injected with medium only. These cell-injected wounds did not perform as well biomechanically as those in unirradiated skin. Irradiating the cells prior to injection resulted in biomechanical results no better than those in medium-injected wounds. CONCLUSIONS These results demonstrate that injection of normal, unirradiated fibroblasts significantly improves healing of the irradiated surgical wound. These cells are likely better able to respond to the proliferative, migratory, and synthetic demands of the wound healing environment, as injection of irradiated cells has an equivalent effect on healing as injection of medium alone.