Numerous studies have shown that geomagnetic activity (GMA) contributes to the development and escalation of cardiovascular disease (CVD), as well as increased morbidity and mortality. However, the underlying molecular mechanisms and approaches for understanding GMA remain unclear. This study aimed to investigate the impact of GMA on oxidative stress and inflammatory responses. Myocardial ischemia/reperfusion injury (MI/RI) rat models were created under various geomagnetic field conditions. The range of cardiac function, markers of myocardial injury, inflammatory factors, and the TLR4/NF-kappa B signaling pathway were measured after the 24-h period. The findings showed that weak GMA significantly improved cardiac function in the MI/RI rat model and reduced the size of myocardial infarction and creatine kinase (CK) and lactic dehydrogenase (LDH) levels. Additionally, weak GMA enhanced superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) content. Furthermore, weak GMA significantly reduced the levels of the myocardial inflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Conversely, the effects observed under severe GMA conditions were opposite to those observed under weak GMA. Western blot and qPCR analysis demonstrated that weak GMA led to a significant downregulation of TLR4, TRAF6, NF-kappa B, TNF-alpha, and MCP-1 in the MI/RI rat models. In contrast to weak GMA, severe GMA increased TLR4, TRAF6, NF-kappa B, and TNF-alpha expression. This study suggested that weak GMA had a limiting effect on MI/RI rat models, whereas severe GMA exacerbated injury in MI/RI rats. These effects were associated with oxidative stress and inflammatory responses and might potentially involve the TLR4/NF-kappa B signaling pathway.