Background <p>Studies have documented that exercise programs have symptomatic relief benefits for ankylosing spondylitis patients. It has also been reported that MGF (Mechanical/Mechano Growth Factor) and related gene expressions can be stimulated by certain exercises. In this study, we explored the possible role(s) MGF could play in controlling arthritis and ankylosing spondylitis-like symptoms in HLA-B27/Hu-β2m transgenic rats.</p> Methods <p>HLA-B27/ Hu-β2m transgenic rats were inoculated with inactivated Mycobacterium tuberculosis to induce arthritis and ankylosing spondylitis, followed by MGF treatment for seven weeks. The animal models were monitored for the onset, severity, and progression of clinical symptoms.</p> Results <p>Our results indicated a dose-dependent increase in the time of onset of arthritis symptoms from 14 days in the control group to 23 days in the high-dose MGF group. Our results also indicated a dose-dependent increase in the anti-inflammatory cytokines IL-2 and IL-10 and decrease in the pro-inflammatory cytokine TNF-α in the peripheral circulation and in bony infiltrations. Likewise, there was a dose-dependent inhibition of STAT3 (signal transducer and activator of transcription 3) and RORγt (retinoic acid-related orphan receptor gamma-t) expression, which was further confirmed by the inhibition of IL-17 expression.</p> Conclusion <p>From the results of our study, it can be concluded that MGF controlled inflammation and inhibited bone erosion and syndesmophyte formation in HLA-B27/Hu-β2m transgenic rats by stimulating IL-2 and IL10 production while downregulating TNF-α, STAT3, RORγt, and IL-17 expression in a dose-dependent manner, leading to a significant reduction in arthritis and AS-like clinical symptoms.</p>