Severe heat stroke (HS) consists of extreme hyperthermia with thermoregulatory failure， leading to high morbidity and mortality. Liver injury is a complication of HS that is associated with inflammatory responses and Kupffer cells (KCs)， which are resident macrophages in the liver that serve as a major source of inflammatory cytokines; however， the association and the underlying mechanisms of KC functions in HS?induced endotoxemia and inflammation require an improved understanding. The important chemokine macrophage inflammatory protein?1α (MIP?1α) increases inflammatory responses and the secretion of inflammatory molecules from KCs， including tumor necrosis factor?α， interleukin (IL)?1β and IL?6. In addition， the activation of c?Jun N?terminal kinase (JNK) signaling is responsible for the development of liver inflammation. Therefore， HS animal and cell models were constructed in order to investigate the pathways involved in the HS?induced dysfunction of KCs. The results of the present study suggest that JNK may be involved in the MIP?1α?associated pathogenesis of KCs in HS injury.