Background Nisoldipine can effectively suppress pulmonary arterial smooth muscle cell proliferation and c-Fos expression. Objective To identify the mechanism of the anti-inflammatory effects in monocrotaline-induced pulmonary arterial hypertension (PAH), focusing on the c-Fos/NLRP3/caspase-1 pathway. Results In a mice model of monocrotaline-induced PAH, miRNA-155 expression was increased. In an in vitro model, overexpression of miRNA-155 promoted inflammation and induced c-Fos, NLRP3, and caspase-1 protein expression. The inhibition of c-Fos reduced the effects of miRNA-155 on inflammation in an in vitro model of monocrotaline-induced PAH. The inhibition of NLRP3 reduced the effects of miRNA-155 on inflammation in an in vitro model of monocrotaline-induced PAH. Conclusions miRNA-155 increased inflammation in monocrotaline-induced PAH through c-Fos/NLRP3/caspase-1.