OBJECTIVE: To investigate the mRNA and protein expression of high mobility group box chromosomal protein 1 (HMGB1) in peripheral blood mononuclear cells (PBMCs) and serum. METHODS: Levels of HMGB1mRNA were detected with reverse transcription polymerase chain reaction (RT-PCR) in PBMC and levels of HMGB1 protein in PBMC and plasm were measured with Western blot in 38 patients with active rheumatoid arthritis (RA), 24 with inactive RA and 20 healthy controls. Ficoll density gradient centrifugation was used to separate PBMCs from peripheral blood. The correlation between the levels of HMGB1 in serum and the index of disease activity in RA was analyzed. RESULTS: There was no statistically significant difference of the mRNA expression of HMGB1 in PBMCs from active RA patients as compared with those from inactive RA group and healthy controls (F = 1.23, P > 0.05). The protein expression of HMGB1 was significantly lower in PBMCs from active RA patients (F = 70.91, P < 0.01), while the protein expression of HMGB1 was higher in plasma from active RA patients (P < 0.001) as compared with that from inactive RA patients and healthy controls. However, there was no statistically significant difference between inactive RA patients and healthy controls (P > 0.05). The level of HMGB1 protein in plasma of RA patients was correlated with erythrocyte sedimentation rate (ESR) (r(s) = 0.478, P < 0.001) and C- reactive protein (CRP) (r(s) = 0.574, P < 0.05). It was not correlated with age, the number of tender joints and swollen joints, radiographic scores and therapeutic effect. CONCLUSION: The protein expression of HMGB1 was significantly decreased in PBMCs from active RA patients, while it was increased in serum from active RA patients. HMGB1 plays a pivotal role in the pathogenesis of RA and may be a target of therapy as a novel cytokine.