The aim of this study is to explore the pathogenesis of granulomatous lobular mastitis (GLM) via pathology and molecular biology. This single-center study included 28 female patients who received a diagnosis of pathologically confirmed GLM from January 2020 to September 2020 at Dongzhimen Hospital of Beijing University of Chinese Medicine. Tissue samples and serum were collected during radical surgery. Western blot and immunohistochemistry were employed to determine caspase-1 and gasdermin D (GSDMD). Transmission electron microscopy (TEM) was used to observe the ultrastructure of cells. Finally, the results were analyzed. The expression of activated GSDMD and caspase-1 were all increased in the lesion group (P < 0.05). The TEM results showed clear features of pyroptosis. We concluded that pyroptosis was important in the development of GLM and inhibitad apoptosis to some degree. The inhibition of pyroptosis response may help to discover new drugs for GLM.