AbstractXanthine oxidoreductase activity (XOR-a) plays an important role as a pivotal source of reactive oxygen species. In the present study, we investigated factors associated with plasma XOR-a in 163 hemodialysis patients (age 67.3 ± 10.9 years; 89 males and 74 females), using a newly established, highly-sensitive assay based on [¹³C₂,¹⁵N₂] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Plasma glucose and serum uric acid levels correlated significantly and positively with plasma XOR-a. In multiple regression analyses, the presence of type 2 diabetes mellitus (T2DM) and plasma glucose were associated significantly, independently, and positively with plasma XOR-a. While serum uric acid correlated significantly and positively with plasma XOR-a in hemodialysis patients without T2DM, plasma glucose and serum glycated albumin, a new marker of glycemic control in diabetic hemodialysis patients, correlated significantly and positively with plasma XOR-a in those with T2DM. Multivariate analyses in those with T2DM revealed that plasma glucose and serum glycated albumin were associated significantly and independently with plasma XOR-a, and that serum uric acid was associated significantly and independently with XOR-a in those without T2DM. Our results suggested that glycemic control in hemodialysis patients may be important in regard to a decrease in ROS induced by XOR.