The negative nitrogen balance after burns is an important factor in the rehabilitation and treatment of burn injury. It is known that the 26s protesome system plays a key role in the protein breakdown of skeletal muscle in some pathological situations, including burns, although the mechanism of which remains poorly understood. The present study surveyed the effect of tumor necrosis factor-alpha (TNF-alpha) on the 26S proteasome sysytem after burn injury, which is thought to be principally responsible for the proteolysis. The means of immuno-precipitation-deduction and enzyme-linked immunosorbent assay were used to test the change of activities and contents of 26S proteasome and 19S regulator in skeletal muscle of mice inflicted with 30% TBSA third-degree burns. The genes expression of 19S regulator's subunits Psmc2, Psmc5, Psmd1, and Psmd2 were examined by the use of reverse-transcription polymerase chain reaction. The results showed that TNF-alpha and burn can markedly increased the activities and contents of 26S proteasome and 19S regulator in mice skeletal muscle. In addition, the expression levels of the 19S regulator's subunits also were remarkably increased. The monoclonal antibody to TNF-alpha obviously can diminish the increment of the activities and contents of 26S proteasome and 19S regulator as much as the expression levels of the 19S regulator's subunits. The results suggested that TNF-alpha can activate the 26S proteasome system in skeletal muscle, thus enhancing the degradation of protein, which is associated with the development of negative nitrogen balance after scald.