Heatstroke continues to be a life-threatening threat during summer time prolonged high temperatures, despite improved treatment and prevention. It’s reported the transient receptor potential vanilloid 4 (TRPV4) inhibitor may safeguard septicemia rodents. Many facets of heatstroke happen to be defined, in the sepsis-mimic in?ammatory reaction to hyperthermia. Hence, TRPV4 can be a therapeutic target for heatstroke. The outcomes in murine types of heatstroke verified that GSK2193874, like a selected TRPV4 inhibitor, was injected at heatstroke onset, after which reduced the decrease in core temperature, the dying rate, wet/dry ratio from the lung, amounts of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, coagulation indicators, the quality of organ injuries, and caspase-3/7 activity (P&lt0.05). But GSK2193874 treatment before heat stress didn’t enhance the signs and symptoms of heatstroke rodents. Therefore, TRPV4 should engage in heatstroke-caused injuries. Timely GSK2193874 administration might be helpful to lessen heatstroke-caused injuries. TRPV4 can be a potential new therapeutic target in fatal heatstroke.