Objective To investigate the clinical manifestations, muscle pathological features, and treatment of inflammatory myopathy with anti-nuclear matrix protein 2 (NXP2) autoantibodies.Methods A retrospective analysis was performed for the clinical manifestations, muscle pathological changes, and treatment methods of four patients with inflammatory myopathy with anti-NXP2 autoantibodies who were treated in our hospital.Results Of all four patients, four had symmetrical proximal limb muscle weakness, two had dermatomyositis-like skin rash, three had dysphagia, and two had edema of extremities. Of all patients, three had a significant increase in serum creatine kinase, and one had normal serum creatine kinase; all four patients had myogenic damage on electromyography and the signal of muscular and fascial edema on muscle magnetic resonance imaging of lower extremities; all four patients had positive anti-NXP2 autoantibodies. Muscle pathology showed that three patients had perifascicular atrophy with perivascular and perimysial inflammatory cell infiltration, and one patient had interstitial edema. All four patients were treated with glucocorticoids; three patients were improved during follow-up, while one patient died accidentally after discharge.Conclusions Dermatomyositis is the main clinical manifestation of inflammatory myopathy with anti-NXP2 autoantibodies, and most patients have dysphagia and edema of extremities. Muscle magnetic resonance imaging of lower extremities shows the signal of muscular and fascial edema. Perifascicular atrophy is the main pathological feature. Glucocorticoids have a good therapeutic effect.