Lasers and electrocautery devices have been applied as an alternative to the scalpel because of better hemostasis and lymphatic sealing. However, previous studies have demonstrated conflicting data regarding the effects of these modalities on the inflammatory response, the first reaction by tissue during wound healing. The purpose of this study is to quantitate inflammatory responses in rat skin following laser, electrocautery, and scalpel injury by measuring T-kininogen (T-KGN), a major acute-phase protein in the rat and its endogenous substrate, cathepsin B, an important inflammatory mediator. Full-thickness wounds (6 cm) were created on the dorsum of Sprague Dawley rats by using a laser, electrocautery, or scalpel. Tissue samples were harvested at 1 hour to 21 days after injury. T-KGN levels were radioimmunoassayed; cathepsin B activity was assayed by using a synthetic substrate Z-Arg-Arg-MCA. Data were analyzed by analysis of variance. T-KGN levels peaked at 3 days for all modalities, although the laser group was statistically (P < or = 0.01) higher at 1, 3, and 7 days after injury. In contrast, cathepsin B activity was significantly (P < or = 0.01) lower at 3 days in the laser group. CO2 laser ablation incites a greater inflammatory response than electrocautery or scalpel injuries. High levels of T-KGN may provide protection from proteolytic damage associated with cathepsins.