Irisin, an adipo-myokine, is positively associated with cardiorespiratory fitness and negatively associated with type 2 diabetes mellitus (T2DM). However, it is unclear if individuals with longer or shorter durations of T2DM express the same irisin levels following exercise. The objective of this study is to investigate the impact of 28 weeks of moderate-to-vigorous intensity aerobic exercise on irisin levels in individuals with short- and long-duration T2DM. This secondary analysis included participants (n=34) aged ≥19 years old with T2DM who completed 28 weeks of aerobic exercise training for 150 minutes per week at a moderate-to-vigorous intensity - 16 weeks at a moderate intensity (4.5 metabolic equivalents of tasks (METs)) and then randomized to 12 weeks of maintained-intensity (4.5 METs) or increased-intensity (6.0 METs) aerobic exercise. Participants were categorized into two groups: 1) short-duration T2DM (<10 years) or 2) long-duration T2DM (≥10 years). Irisin was analyzed using enzyme-linked immunosorbent assay and western blotting techniques. All measurements were performed at baseline, 16 weeks, and 28 weeks. A significant time x T2DM duration group interaction (F(2)=8.062, p<0.01) was observed with 28 weeks of moderate-to-vigorous intensity aerobic exercise. Western blot analysis revealed a 1.37-fold increase in plasma irisin expression (p=0.03) in the long-duration increased-intensity group and no change in irisin expression (p>0.05) in the maintained-intensity groups of short- and long-duration. The results of this analysis suggest that 28 weeks of moderate-to-vigorous intensity aerobic exercise differently impacted plasma irisin in individuals with short- or long-duration T2DM.