Background. Burn injury often causes multiple organ failure as well as skin damage. Several studies suggest that TNF-α plays an important role in postinjury immunosuppression by altering lymphoid tissues. We investigated the regulation of TNF-α expression and apoptosis in the spleen and thymus of mice after burn injury.Materials and methods. C57BLKS/J mice were subjected to 18% TBSA full-thickness burn and the spleen and thymus were harvested at various time points (3 h to 29 days). The expression of TNF-α mRNA and protein in tissue extracts was analyzed by RT-PCR and ELISA. Apoptosis was measured by flow cytometry using annexin V staining.Results. Burn injury induced TNF-α mRNA expression in the thymus at Day 1 and it returned to the basal levels at Day 14 and thereafter. Similarly, TNF-α mRNA up-regulation peaked between Day 1 and Day 3 in the spleen. Induction of TNF-α protein peaked at Day 1 in the thymus, whereas, TNF-α protein was unchanged in the spleen after burn injury. There was a twofold increase in apoptotic cells at Day 1 in the thymus, which is consistent with mRNA and protein data. In contrast, burn injury did not change apoptotic events in the spleen.Conclusions. The parallel induction of TNF-α mRNA, TNF-α protein, and apoptosis suggests that TNF-α may contribute to immunosuppression after burn injury by inducing apoptosis in the thymus.