Previous clinical studies reported elevated semicarbazide-sensitive amine oxidase (SSAO) activity in insulin-dependent diabetes mellitus (IDDM), but there are not sufficient data about SSAO in non-insulin-dependent diabetes mellitus (NIDDM). The present study was conducted to investigate serum SSAO activity in NIDDM patients compared with nondiabetic and IDDM patients. Serum SSAO activity in 61 patients with diabetes (n = 34 NIDDM and n = 27 IDDM) and 36 controls was determined using ¹⁴C-benzylamine as a substrate. NIDDM and IDDM patients exhibited higher SSAO activity compared with controls ([mean ± SD] NIDDM, 164.60 ± 69.43 pmol/mg protein/h, P < .0001; IDDM, 143.91 ± 72.45 pmol/mg protein/h, P < .002; control, 91.46 ± 28.11 pmol/mg protein/h). There was a significant positive correlation between serum SSAO activity and the body mass index (BMI), body weight, hemoglobin A_1C (HbA_1c), fasting plasma glucose, and triglycerides. Within the control group, SSAO correlated with total cholesterol levels. The progression and severity of diabetic complications such as angiopathy may be exacerbated by cytotoxic metabolites (eg, formaldehyde and hydrogen peroxide) formed by SSAO. These results reveal the possibility that elevated serum SSAO activity in association with obesity and hyperlipidemia may be a cardiovascular risk factor in diabetes mellitus.