CitH3 is a sensitive and long-lasting biomarker compared to PCT, IL-1β and IL-6 in LPSS. Mice were intraperitoneally administrated LPS (35 mg/kg) with or without YW3-56. Sera were prepared at 0.5, 3, 12 and 24 hours after LPS for measurement of CitH3 (A), PCT (B), IL-1β (C) and IL-6 (D) by ELISA. (A) Circulating CitH3 was detected quickly (0.5 hour), accumulated maximally at 12 hours, and sustained for 24 hours. YW3-56 significantly attenuated LPS-induced increase of CitH3. *p < 0.05 compared to DMSO, #p < 0.05 compared to 12 hours post LPS. (B) LPS could not induce a significant increase of PCT in blood in the early stage of endotoxic shock (0.5, 3 and 12 h) till 24 hours compared to DMSO group (p < 0.0001). (C and D) Pro-inflammatory cytokines irregularly fluctuated after LPS administration (IL-1β & IL-6). They did not respond to LPS early (IL-1β), although they were attenuated by YW3-56 treatment. Data was shown as mean ± standard deviation (SD) (n = 3–5/group). IL-1β: interlukine-1β; IL-6: interlukine-6; CitH3: Citrullinated histone H3; LPS: Lipopolysaccharide; DMSO: dimethyl sulfoxide. PCT: procalcitonin; LPSS: LPS-induced endotoxic shock.