OBJECTIVES: The objectives of this study were to examine the correlation between the level of serum inflammatory markers and the stability of carotid plaques in patients with ischemic cerebrovascular disease and to assess the ability of each inflammatory marker to identify vulnerable carotid plaques. METHODS: For the early identification of vulnerable carotid plaques, 65 patients with carotid plaques were divided into a stable plaque group (n = 21) and an unstable plaque group (n = 44) according to magnetic resonance imaging characteristics. The unstable plaque group was divided into an unstable unruptured plaque group (n = 29) and an unstable ruptured plaque group (n = 15) according to whether the fibrous cap was ruptured. The levels of serum soluble cluster of differentiation 40 ligand (sCD40L), matrix metalloproteinase (MMP)-9, and MMP-2 were measured by enzyme-linked immunosorbent assay. RESULTS: The levels of serum sCD40L and MMP-9 in the unstable plaque group, the unstable unruptured plaque group and the ruptured plaque group were significantly higher than those in the stable plaque group (P < 0.05). There was no significant difference in the MMP-2 level between the stable plaque group and unstable plaque group (P = 0.056). The MMP-2 levels in the stable plaque group, unstable unruptured plaque group, and ruptured plaque group were not different (P = 0.095). The carotid plaques and the positive rate of MMP-9 of >= 84.09 ng/mL were statistically significant, suggesting increased vulnerability. CONCLUSIONS: Serum levels of sCD40L and MMP-9 are associated with the stability of carotid plaques. Higher levels of serum sCD40L and MMP-9 may suggest that the plaques are vulnerable or have ruptured.