To identify new biomarkers for significant carotid stenosis, we compared the serum proteome in patients with significant carotid stenosis before and after carotid stenting. We used mini-gel technology in a two-dimensional electrophoresis procedure and mass spectrometry in ten patients. Twenty six proteins were differently expressed before and after carotid stenting. Of them, thirteen proteins decreased significantly after carotid stenting. These proteins included complement component 3, fibrinogen gamma, hemopexin precursor, chronic lymphocytic lymphoma (CLL)-associated antigen KW-4 splice variant 2, novel protein, plectin 1 isoform 6, carboxypeptidase N polypeptide 1 50 KD, apolipoprotein L, unnamed protein product, PMS1 protein homolog 2, sister of mammalian grainhead protein isoform 1, KIAA0184 protein, and gelsolin isoform b. Twelve of 28 differently expressed proteins increased significantly after the carotid stenting. These proteins were zinc finger protein, alpha-2 macroglobulin, angiotensinogen, chain B antithrombin, chain E fragment Double-D from human fibrin, complement component C4, dynein axonemal heavy polypeptide 3, preapolipoprotein E, kinesin-like 8 isoform B, macrophin 1 isoform 2, hypothetical protein from EUROIMAGE1967720, and LOMP protein. Our preliminary study showed that twenty eight proteins were differently expressed before and after the carotid stenting. These results suggest that these proteins, especially proteins decreased after the carotid stenting, can be used as useful biomarkers for diagnosing significant carotid stenosis.