Objective To investigate the relationship between the effect of high mobility group protein box 1 (HMGBI) on the renal injure of systemic lupus erythematosus (SLE) and the expression of Toll-like receptor 4(TLR4). Methods The level of HMGB1, MMP-2 and TIMP-2 in serum from 16 pa-tients with SLE, 18 patients with lupus nephritis(LN) and 12 healthy people were measured by ELISA. The fresh peripheral blood mononuelear cell (PBMC) were isolated and the total RNA was extracted. Then the mRNA expression of HMGB1 was amplified by RT-PCR. Flow cytometry analysis was performed to study cell surface markers and the expression of TLR4. Results RT-PCR and ELISA results showed that the expres-sions of mRNA and level of HMGB1 protein in serum were higher in patients with LN than those in SLE and healthy people. The expression of TLR4 in CD14+ monecytes of patients with LN was higher than that with SLE and healthy people, while there were no significance in CD3+ T cells among LN, SLE and healthy peo-ple. The expressions of MMP-2 and TIMP-2 in serum of LN was lower than that in SLE and healthy people, at the same time the ratio of MMP-2/TIMP-2 decreased in LN group. HMGB1 mRNA and CD14+/TLR4+ was negatively correlated with the ratio of MMP-2/TIMP-2, and the level of HMGB1 in serum was positively correlated with proteinuria, while negatively correlated with the ratio of MMP-2/TIMP-2 in LN. Conclusion HMGB1 is one of the important cytokine in the pathogenesis of lupus nephritis. HMGBI might play a role in proteinuria of lupus nephritis in part via TLR4 pathway to activate monocytes and decrease the expression of MMP-2/TIMP-2.