The present study investigated the expression of thioredoxin (TRX), an important anti-oxidative protein, and its relationship to plaque instability in atherectomy specimens from 43 and 42 patients with stable (SAP) and unstable (UAP) angina pectoris, respectively. We histologically assessed thrombus formation, cellular elements, localization of TRX and of oxidized low density lipoprotein (ox-LDL), intraplaque hemorrhage, and transition metal iron (Fe(2+), Fe(3+)) deposition in these specimens. The clinical characteristics of the two groups did not differ except for aspirin administration. The incidence of thrombus formation was more frequent (P=0.005) and immunopositive areas of macrophage, TRX and ox-LDL were significantly larger in patients with UAP than SAP (P<0.001, each). Macrophages were mainly immunoreactive for TRX and ox-LDL. Intraplaque hemorrhage evaluated by glycophorin A immunoreactivity and Fe(2+)/Fe(3+) deposition was also more obvious in lesions from patients with UAP than SAP (P<0.001, each). Additionally, immunopositive areas of TRX and ox-LDL positively correlated with Fe(2+)/Fe(3+) deposition and were also associated with thrombus formation. Although the underlying mechanisms remain unknown, TRX was up-regulated in response to increased oxidative stress and associated with intraplaque hemorrhage of coronary culprit lesions, and thus might be a potent marker of plaque instability.