N-acetyl-beta-D-glucosaminidase (NAG) is released from lysosomes, but the clinical significance of its serum activity in the pathogenesis of coronary artery disease has not been well understood. We measured serum NAG activity by a colorimetric method in consecutive 168 patients suspected of having coronary artery disease who underwent diagnostic coronary angiography. In addition, we evaluated the relationship between the activity and severity of coronary artery disease, as well as various coronary risk factors. Serum NAG activity was higher in the multi-vessel disease group than in the no stenotic lesion group (9.2+/-2.3 vs. 7.8+/-1.8 U/l, P<0.01) and in the single-vessel disease group (vs. 8.2+/-2.2 U/l, P<0.05). In all patients, Gensini score was closely correlated with the serum NAG activity (r = 0.39, P<0.001). Multiple regression analysis showed that serum NAG activity was correlated with plasma insulin level (r = 0.49, P<0.01), but not correlated with other coronary risk factors. In 126 patients without apparent diabetes mellitus, serum NAG was also correlated with plasma insulin level (r = 0.37, P<0.01) and additionally with insulin resistanc determined by homeostasis model assessment (r = 0.47, P<0.01). Our results suggested that serum NAG activity correlates with the severity of coronary artery disease in relation to plasma insulin level and insulin resistance, and thus can be an indicator of coronary artery disease based upon abnormalities of glucose metabolism.