Abstract: Objective：To investigate the clinical significance of S100A8/A9, Toll-like receptor 4 (TLR4) and matrix metalloproteinase (MMP-2) levels in peripheral venous serum of patients with multiple sclerosis (MS). Methods：Totally 16 cases of MS patients were selected as MS group, and 16 cases of healthy people as control group. The serum samples were detected by protein chip detection method to quantificationally analyze the changes of serum S100A8/A9, TLR4 and MMP-2 levels. Results：The serum of S100A8/A9, TLR4 and MMP-2 levels in MS group were significantly higher than which in control group (P＜0.01); The three indicators in MS patients showed significant correlations (P＜0.05). Conclusions：The expression of S100A8/A9, TLR4 and MMP-2 in the serum of patients with clinical MS is upregulated, suggesting that they might be involved in the pathogenesis of MS. Combined detection of serum S100A8/A9, TLR4 and MMP-2 levels may provide a new way of thinking for the diagnosis, treatment and judgment of state in clinical MS.