Abstract: Objective To study the changes in subeschar fluid and plasma TNF-α in rabbits with severe burns in response to early administration of imipenem (IPM). Methods Sixteen rabbits with severe burns were randomized into 2 two equal groups to receive treatment with 100 mg (100 ml) of IPM q8 h×3 days and equivalent volume of saline, respectively. The levels of TNF-α in the subeschar tissue fluids and plasma were determined by double-antibody sandwich enzyme-linked immunosor- bent assay (ELISA) after the first initial dose of 100 mg of imipenem/cilastatin, lasting 3 days. Results The plasma TNF-α levels in rabbits increased after the burn injury, reaching the peak level 16 h postburn and sustained the high levels till 72 h. At the same time point, TNF-α levels in the subeschar tissue fluids increased evidently in comparison with the plasma level, but both were lowered with early administration of imipenem (P<0.05). Conclusion Subeschar and plasma levels of TNFα can be significantly lowered with early-stage administration of imipenem, suggesting that IPM inhibits the release of TNFα and endotoxin to relieve or prevent endotoxemia after sever burn injury in rabbits.