BACKGROUND After hemorrhagic shock, macrophages are less responsive to lipopolysaccharide (LPS) regarding cytokine production and receptor expression. However, mechanisms responsible for this are poorly understood. Suppressors of cytokine signaling (SOCS) proteins have been found to play a prominent role in LPS tolerance and cytokine desensitization in macrophages. Therefore, the purpose of this study was to determine whether hemorrhagic shock induced SOCS expression. METHODS Male C3H/HeN mice were subjected to hemorrhage or sham hemorrhage. Twenty-four hours after each procedure, tissues were harvested, the cells were processed for protein, and SOCS expression was examined. RESULTS Our data show that SOCS-1 expression does not change after hemorrhage, but SOCS-3 is up-regulated in a tissue and cell population (e.g., macrophage)-specific manner. CONCLUSION These data suggest that cytokines or other inflammatory mediators present during the first 24 hours after the induction of shock have the ability to induce tolerance to LPS or cytokines and suppress the function of immune cells by up-regulating SOCS-3.