Plasma cell mastitis (PCM) is a type of non-lactational mastitis characterized by dilated mammary ducts and plasma cell infiltration as its main pathological features. The etiology of PCM remains unclear, and current treatments, including antibiotics, anti-tuberculosis drugs, hormones, and surgery, have shown limited efficacy. These treatments often result in significant physical and mental damage to female patients due to drug side effects, postoperative disfigurement, and recurrences. It is crucial to further investigate the pathogenesis of PCM to develop precise and effective treatments and reduce recurrence rates. Most scholars believe that the accumulation and leakage of fatty substances within the mammary ducts lead to chemical irritation and immune responses around the ducts, resulting in the infiltration of various inflammatory cells. The accumulation of mammary duct secretions may be related to abnormal material exchange in mammary duct epithelial cells, ultimately causing epithelial cell necrosis. Substance exchange channels facilitate the transfer of materials between cells while maintaining homeostasis in the internal environment. Recent studies indicate that these channels are closely related to inflammation and immunity. Ion channels are involved in physiological and pathological responses in the mammary gland through mechanisms such as regulating ion-water balance and initiating immune responses. The mechanosensitive ion channel Piezo1 acts as a force sensor in chronic inflammation associated with mechanical force. Exploring how mechanical injury and a firm environment induce the secretion of pro-inflammatory factors and the migration of inflammatory cells may provide insights into the local inflammatory response in PCM following trauma. Aquaporins (AQPs) dynamically regulate water and solute transport. The rapid swelling and liquefaction of local PCM lesions might result from fast water flow changes mediated by AQPs and inflammation involving both innate and adaptive immunity. Some AQPs exhibiting a glycerol transport capacity play roles in lipolysis and lipid deposition, offering insights into the accumulation of lipid-like secretions in PCM ducts. Extracellular vesicles (EVs) encapsulate and transport various biomolecules, protecting them from degradation in harsh extracellular environments and facilitating short- and long-distance communication. When carrying pro-inflammatory content, EVs can spread destructive inflammation, explaining the PCM breast accompanied by systemic inflammatory reactions such as fever, cough, and erythema nodosum of the lower limbs. PCM patients exhibit secretion accumulation in the ducts, significant ductal dilation, and extensive inflammatory cell infiltration around the ducts. Abscesses containing a large number of necrotic cells and tissue debris can lead to fistula formation if treatment is delayed and the condition persists. This paper explores the pathogenesis of PCM from the perspective of substance exchange channel disorders, including ion channels, AQPs, and EVs, aiming to provide new insights for future research on key pathological mechanisms and intervention targets in PCM.