Omentin-1 is an adipokine implicated in diabetes, inflammation, and cardiovascular disease. However, no prospective studies have examined the impact of circulating omentin-1 levels on arterial stiffening in patients with type 2 diabetes mellitus. For the purpose of this study, we recruited 120 patients with type 2 diabetes mellitus and measured serum omentin-1, adiponectin, and high-sensitivity C-reactive protein levels as well as other cardiovascular risk factors. Arterial stiffness was assessed by brachial ankle pulse wave velocity (baPWV). An increase in the level of circulating omentin-1 over a period of 1 year was positively correlated with changes in levels of HbA1c and serum adiponectin as well as baPWV. Subjects with higher baseline serum omentin-1 levels tended to have a reduced arterial stiffness after 1 year (P for linear trend = 0.03). In the group with increased baPWV after 1 year, the magnitude of increase of circulating omentin-1 levels was significantly higher than in the group with a lower baPWV after 1 year (134.3 [16.6, 277.1] ng/mL vs. 15.9 [-67.6, 145.7] ng/mL, P < 0.01). Multiple stepwise logistic regression analysis revealed that an increase in systolic blood pressure and an increase in serum omentin-1 level were independently correlated with arterial stiffening, even after adjusting for other cardiovascular risk factors and medication history. Baseline serum omentin-1 levels can predict arterial stiffness changes occurring within a year. Furthermore, changes in serum omentin-1 levels after a year can function as independent markers of arterial stiffening in patients with type 2 diabetes mellitus.