Background: Immune-mediated necrotizing myopathy (IMNM) is a relatively new proposed category of idiopathic inflammatory myopathies (IIMs), characterized by the presence of abundant necrotic muscle fibers, myophagocytosis, and sparse inflammatory infiltrates. The aim of our study was to analyze the immunopathological characteristics of IMNM by detecting biopsy samples from a cohort of patients, and to delineate the pathways involved in the pathogenesis. Material/Methods: A retrospective evaluation of muscle biopsy samples, clinical and laboratory data, and immunohistochemical analysis of macrophages MHC-I and MAC, was performed for all patients diagnosed as having IMNM but without a prior exposure to statins. Results: Immunohistochemical analysis revealed the presence of CD68(+) macrophages mainly in the necrotic muscle fibers and the endomysial connective tissue. MHC-I and MAC positively stained not only the necrotic fibers or vessels but also the non-necrotic ones. Conclusions: Our data describe general immunological features in IMNM patients, which may be helpful in serving as bio-markers, aid in diagnostic decisions, and provide clues into the underlying mechanisms involved in this disease.