<p>MicroRNA-146a (miR-146a) is an important regulator of inflammation and insulin sensitivity in obesity and type 2 diabetes mellitus (T2DM). Changes in miR-146a expression in obesity and diabetes are tissue- and disease-context dependent; however, most studies have consistently reported reduced miR-146a expression in T2DM. Reduced miR-146a expression in T2DM contributes to chronic inflammation and metabolic dysfunction, whereas its expression in obesity appears to be more variable and context-dependent. Physical activity modulates miR-146a expression, with high-intensity interval training, resistance training, and combined aerobic–resistance exercise generally increasing its levels and suppressing NF-κB-mediated inflammation. In contrast, long-term exercise may normalize elevated miR-146a expression in obesity by reducing inflammatory burden. These changes are associated with improvements in insulin sensitivity, lipid metabolism, and vascular function. Overall, miR-146a may serve as both a biomarker and a mediator of the anti-inflammatory and metabolic benefits of exercise, although its response depends on exercise characteristics and individual physiological status.</p>