Sepsis is asevere, systemic inflammatory disease caused by various kinds of microbes. In the present study, we immunohistochemically examined tumor necrosis factor (TNF)-α expression in sepsis-induced lung injury, and discuss its availability for the postmortem diagnosis of sepsis. Lung samples were obtained from different lung lobes of nine sepsis and eight control cases with postmortem intervals between 12 and 48 hours. Immunohistochemical analysis using anti-human TNF-α rabbit polyclonal antibodies was carried out. In sepsis and control groups, immunoreactivity for TNF-α was strongly detected in round-shaped mononuclear cells. The intensity of the immunohistochemical staining reaction was homogeneous in all lobes of the lungs examined. Furthermore, a double-color immunofluorescence analysis revealed that macrophages were a main cellular source of TNF-α in the lungs. To semiquantitatively evaluate the expression of TNF-α in the lungs, the ratios of the number of TNF-α-positive macrophages to total number of macrophages were calculated. Morphometrically, in lungs of the sepsis group, the ratio of TNF-α-positive macrophages was significantly higher, compared with the control group. TNF-α expression in the lungs can become a clue for the postmortem diagnosis of pulmonary inflammation, especially, TNF-α-positive ratios of 20% of more might suggest sepsis as the cause of death.