Background: Type 2 diabetes mellitus (T2DM) promotes pulmonary fibrotic remodeling through activation of transforming growth factor-beta 1 (TGF-β1)-dependent signaling, myofibroblast differentiation, and excessive extracellular matrix (ECM) deposition. Exercise training may attenuate these molecular alterations; however, comparative evidence regarding aerobic and combined exercise remains limited.

Methods: Fifty male Wistar rats were randomly allocated to four experimental groups: healthy control, diabetic control, diabetic plus aerobic exercise, and diabetic plus combined exercise. T2DM was induced by a high-fat diet followed by streptozotocin administration. Both exercise interventions were performed for 12 weeks. Pulmonary mRNA expression of TGF-β1, collagen type I alpha 1 (Col1a1), and alpha-smooth muscle actin (α-SMA) was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Data were analyzed using one-way ANOVA followed by Tukey's post hoc test.

Results: Diabetes significantly increased the expression of TGF-β1, Col1a1, and α-SMA compared with healthy controls (P < 0.001). Both aerobic and combined exercise significantly attenuated the diabetes-induced upregulation of these fibrogenic genes (P < 0.001). The reduction in Col1a1 and α-SMA expression was more pronounced following combined exercise than aerobic training. Exercise interventions also improved fasting blood glucose and partially restored body weight compared with diabetic controls.

Conclusion: Both aerobic and combined exercise effectively attenuated diabetes-associated transcriptional activation of pulmonary fibrogenic markers, with combined exercise demonstrating superior regulation of genes involved in extracellular matrix remodeling and myofibroblast activation. These findings suggest that combined exercise may provide greater protection against diabetes-related pulmonary fibrotic remodeling, although confirmation through protein, histological, and functional analyses is warranted.