Objective To explore the correlation of serum matrix metalloproteinase-2 (MMP-2) and tissue metalloproteinase inhibitor-2 (TIMP-2) levels to carotid atherosclerosis plaque vulnerability in patients with anterior circulation infarction. Methods Sixty patients with anterior circulation infarction and 38 healthy volunteers were enrolled in this study. Color Doppler ultrasonography of the carotid artery was performed to determine the carotid intima-media thickness (IMT), Crouse plaque integral (CPI) score, and the total carotid plaque area (CPA). According to the nature of the carotid atherosclerosis plaque defined by ultrasonography, the patients were divided into vulnerable plaque (VP) group (33 cases), stable plaque (SP) group (27 cases), and no plaque (NP) group (38 cases). Serum MMP-2 and TIMP-2 levels were detected in these subjects using enzyme-linked immnosorbent assay (ELISA). Results Ultrasonography showed significantly greater/MT, CPI and CPA in VP group than in SP and NP groups (P<0.05). Serum MMP-2 level was significantly elevated in VP group as compared with that in SP and NP groups (P<0.05). Serum TIMP-2 level was significantly lower in VP group than in SP and NP groups (P<0.05). In VP group, serum MMP-2 level and MMP-2/TIMP-2 ratio were found to positively correlate to IMT, CPl and CPA (r=0.961, 0.966, and 0.804 for MMP-2, respectively, P<0.05;r=0.625, 0.709, and 0.651 for MMP-2/TIMP-2 ratio, respectively, P<0.05), while TIMP-2 was inversely correlated to IMT, CPI and CPA (r=-0.944, -0.996, and -0.859, respectively, P<0.05). Conclusion Serum MMP-2 and TIMP-2 levels and MMP-2/TIMP-2 ratio are closely correlated to carotid atherosclerosis plaque vulnerability.