To explore the roles of mesenteric lymph on lung injury in heatstroke (HS), HS rat model was prepared in a prewarmed incubator. Vascular endothelium injury biomarkers (circulating endothelial cell [CEC] as well as von Willebrand factor [vWF] and thrombomodulin [TM]), proinflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6, and high mobility group box 1), and coagulant markers (activated partial thromboplastin time, prothrombin time, D-Dimer, and platelet count) were tested in HS and HS with mesenteric lymph duct ligation (LDL) rats. In addition, lung histopathology; arterial blood gas; Evans Blue dye (EBD) and protein lung permeability; intralung inflammatory parameters including bronchoalveolar lavage fluid (BALF) TNF-α, IL-1β, and IL-6 levels; myeloperoxidase (MPO) activity; and vWF immune staining were analyzed. LDL prolonged HS onset time but not HS survival time. LDL significantly attenuated endothelial cell injury for decreased CEC counts as well as plasma vWF and TM concentrations; downregulated systemic inflammation for decreased plasma TNF-α, IL-1β, IL-6, and high mobility group box 1 levels; and ameliorated coagulant disorders for decreased activated partial thromboplastin time, prothrombin time, and D-Dimer levels as well as increased platelet counts. LDL also significantly reduced acute lung pathological injury; improved lung function indexes including arterial blood PaO2, pH, PaCO2, and lactic acid; decreased BALF TNF-α, IL-1β, and IL-6 levels and lung MPO activity; improved EBD and protein lung permeability; and inhibited lung vascular endothelium vWF expression. However, all of these parameters were not recovered to the normal states. In summary, LDL developed protection roles systemically and alleviated lung injury in HS rats which indicated that modulating mesenteric lymph flow may have some potential benefits in HS.