Sustained inflammation is associated with pulmonary vascular remodeling and arterial hypertension (PAH).Serum-glucocorticoid regulated kinase 1 (SGK1) has been proven to participate in vascular remodeling, but its role in inflammation-associated PAH remains unknown.In this study, we investigated the importance of SGK1 expression and activation to monocrotaline (MCT)-induced PAH, an inflammation-associated experimental model of PAH.The expression of SGK1 in lungs of MCT-induced PAH rats was significantly increased.SGK1 knockout mice were resistant to MCT-induced PAH and showed less elevation of right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in response to MCT injection.Inhibition of SGK1 activity with its inhibitor, EMD638683, also prevented the development of MCT-induced PAH.EMD638683 treatment suppressed macrophage infiltration and inhibited the proliferation of pulmonary arterial smooth muscle cells (PASMCs) in lungs of MCT-induced PAH rats.The expression of SGK1 was primarily in alveolar macrophages.Coculture of wild-type macrophages promoted proliferation of PASMC in vitro, while macrophages derived from SGK1 knockout mice or treated with EMD638683 failed to induce this response.Collectively, our results demonstrate that SGK1 is important in regulating macrophage activation to contribute development of PAH, thus SGK1 could be a therapeutic target of PAH.