Objective To study endotoxin release induced by differential antibiotics in gram negative bacterial infection. Methods Thirty critical patients accompanied with gram negative bacterial infection were divided into group A (imipenem group, n=15) and group B (ceftazidine group, n=15). Imipenem (0.5 g iv q8h) and ceftazidine (1.0 g iv q8h) were given respectively. White blood cell (WBC), systolic blood pressure (SBP), lipopoly sacchride (LPS), tumor necrosis factor alpha (TNFα) and high density lipoprotein (HDL) were determined in 0, 1, 2, 3, 5 and 7 day. Results There was no difference in the change of WBC between two groups. Group A had a more stable SBP than group B. There was lower endotoxin release in group A than in group B and so were the cytokines release. HDL level was lower in group B than in group A. Conclusion Imipenem has lower endotoxinliberating potential than ceftazidine and mediate lower cytokines release. HDL may protect the patients from LPS damage.