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Introduction: Some cytokines, including asprosin and brain-derived neurotrophic factor (BDNF), are metabotropic factors, which play a role in the development of type 2 diabetes. This study aimed to determine the effect of aerobic interval training on the circulating levels of BDNF and asprosin in men with type 2 diabetes. Material & Methods: In this semi-experimental study, 20 men with type 2 diabetes were selected by random sampling and randomly divided into two experimental and control groups. Exercise training was performed for 12 weeks (three 60-90-min sessions of interval aerobic training). The obtained data were analyzed in SPSS software (version 26) through t-test and ANCOVA (P≤0.05). Findings: The results showed that after the training intervention, a significant decrease was observed in serum asprosin level (F=7.670; P=0.013), followed by a significant increase in serum levels of BDNF (F=7.585; P=0.014) in the training group, compared to the baseline values and the control group. Discussion & Conclusion: According to the results of the present study, it can be said that interval aerobic training has an effective role in controlling blood glycemic levels and the treatment of type 2 diabetes by reducing asprosin and increasing BDNF as two metabotropic cytokines.