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Objective: To investigate the effect of high mobility group protein 1 (HMGB1) antagonist BoxA via tail vein injection on the improvement of clinical signs and anti-inflammatory effects in a rat model of bacterial meningitis (BM). Methods: Male Sprague-Dawley (SD) rats were used and the normal rats were set as the control group (n=20). Another sixty rats were injected with Es- cherichia coli (DH5α1× 107 CFU/mL) to establish BM rat model and then were randomly divided into two groups (n=30): after anesthesia one group received intravenous BoxA (BoxA group), the other one received PBS injection as placebo (Vehicle group). Three days after model establishment, the clinical index of each group and pathophysiological parameters (intracranial pressure and CSF white blood cells (WBC) count) were evaluated, Enzyme-linked immunosorbent assay (ELISA) method were used to detect the relative serum HMGB1 content, Evans blue staining were used to observe the blood-brain barrier (BBB) permeability, immunofluorescence staining were used to detect the expression level of cerebral inflammation cytokines (IL-1β and TNF-α). Results: Compared with Control group, clinical indicators, intracranial pressure, WBC count and serum HMGB1 content in Vehicle group has significantly increased (P<0.05). These changes were partially reduced in the BoxA group compared to the Vehicle group (P<0.05). In addition, Vehicle group showed increased EB leakage and increased expression of inflammatory factors (IL-1β and TNF-α) than Control group (P<0.05). These changes were also partially adjusted in the BoxA group compared to the Vehicle group (P<0.05). Conclusion: Tail vein injection of HMGB1's inhibitor BoxA can down-regulate HMGB1 expression and alleviate the clinical symptoms and inflammatory responses in BM rats. [ABSTRACT FROM AUTHOR]