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Stroke is an important global health concern. The most prevalent infectious complication after stroke is stroke-associated pneumonia (SAP), which severely impairs recovery of neurological function and has an adverse impact on the prognosis. However, the pathogenesis of SAP is largely unknown. We established a model of SAP by middle cerebral artery occlusion/reperfusion (MCAO/R) and identified spontaneous pneumonia in mice with MCAO/R by staining the lung tissue with hematoxylin-eosin and measuring the bacterial load in the lungs and expression levels of inflammatory factors in plasma. We also confirmed expression of repulsive guidance molecule A (RGMa) in splenic mononuclear cells (SpMNCs) following MCAO/R surgery. Recombinant mouse RGMa protein, propranolol, and the glucocorticoid receptor blocker RU486 were administered to investigate the effects of RGMa on SAP and elucidate the underlying mechanism. Marked spontaneous pneumonia was observed in the mice that had undergone MCAO/R. RGMa expression in SpMNCs from these mice was significantly reduced at 24 and 72 h following MCAO/R surgery. Exogenous administration of recombinant mouse RGMa markedly attenuated spontaneous pneumonia in MCAO/R mice. After administration of propranolol, there was a significant increase in the expression level of RGMa in SpMNCs and amelioration of spontaneous pneumonia in these mice. Administration of RU486 did not significantly change the RGMa expression level or ameliorate spontaneous pneumonia. RGMa attenuated spontaneous pneumonia in mice that had undergone MCAO/R. The underlying mechanism may involve regulation of sympathetic excitation. RGMa may play a key role in SAP.