Objective: To study the mechanism of macrophage injury after trauma-hemorrhagic shock. Methods: Wistar male rats underwent trauma (closed bone fracture) and hemorrhage (mean arterial blood pressure of 35 mm Hg±5 mm Hg for 60 minutes, following fluid resuscitation). Rats without trauma, hemorrhage or fluid resuscitation served as controls. Peritoneal macrophages were harvested at 6 hours and 1, 2, 3, 7 days after traumatic hemorrhagic shock to determine the effects of pertussis toxin (PTX, as a specific inhibitor to Giα) and cholera toxin (CTX, as a stimulant to Gsα) on macrophage-Ia expression and TNF-α production and levels of Giα and Gsα. Results: The macrophages from the injured rats revealed a significant decrease of Ia positive number and TNF-α release in response to LPS. With pretreatment with PTX 10-100 ng/ml Ia positive cells and LPS-induced TNFα production in both control and impaired macrophages populations were dose-dependently increased. Both macrophages populations were not responding to CTX treatment (10-100 ng/ml). Western blot analyses showed that the levels of Giα protein expression increased as much as 116.5%- 148.8% of the control level from 6 hours through 7 days after traumatic hemorrhage. The levels of Gsα protein expression were reduced at 6 hours and decreased to the lowest degree; 36% of the control at day 1, began to return at day 2 and returned to the normal level at day 7, following traumatic hemorrhagic shock.Conclusions: PTX-sensitive G-protein may participate in the modulation of macrophage-Ia expression and TNF-α release following traumatic hemorrhagic shock. Analyses of the alteration of Giα and Gsα protein expressions further supports the concept that G-protein is involved in trauma-induced macrophage signal transduction pathways. Objective: To study the mechanism of macrophage injury after trauma-hemorrhagic shock. Methods: Wistar male rats underwent trauma (closed bone fracture) and hemorrhage (mean arterial blood pressure of 35 mm Hg ± 5 mm Hg for 60 minutes, following fluid resuscitation) . Rats without trauma, hemorrhage or fluid resuscitation served as controls. Peritoneal macrophages were harvested at 6 hours and 1, 2, 3, 7 days after traumatic hemorrhagic shock to determine the effects of pertussis toxin (PTX, as a specific inhibitor to Giα) and cholera toxin (CTX, as a stimulant to Gsα) on macrophage-Ia expression and TNF-α production and levels of Giα and Gsα. Results: The macrophages from the injured rats revealed a significant decrease of Ia positive number and TNF-α release in response to LPS. With pretreatment with PTX 10-100 ng / ml Ia positive cells and LPS-induced TNFα production in both control and impaired macrophages populations were dose-dependently increased. Both macrophages The populations were not responding to CTX treatment (10-100 ng / ml). Western blot analysis showed that the levels of Gi [alpha] protein expression increased as much as 116.5% - 148.8% of the control level from 6 hours through 7 days after traumatic hemorrhage. The levels of G protein alpha were reduced for 6 hours and decreased to the lowest degree; 36% of the control at day 1, beginning to return at day 2 and returned to the normal level at day 7, following traumatic hemorrhagic shock. Conclusions: PTX-sensitive G-protein may participate in the modulation of macrophage-Ia expression and TNF-α release following traumatic hemorrhagic shock. Analyzes of the alteration of Giα and Gsα protein expressions further supports the concept that G-protein is involved in trauma-induced macrophage signal transduction pathways.