Objective To explore the preventive effect of Shengmaiyin on coagulation dysfunction of exertional heatstroke(EHS) in rat. Methods Fifteen SPF male SD rats were randomly divided into sham operation group, heatstroke group, and Shengmaiyin group (5 each group) after implantation of telemetry temperature capsule for one week. Rats in Shengmaiyin group were given Shengmaiyin at 0.02 ml/(g·d) by gavage for five days. The rats in the heatstroke group and Shengmaiyin group ran in the artificial climate chamber (40 ℃, 70% humidity). The running time and distance were recorded when the core temperature reached 42 ℃. Blood samples from the three groups of rats were collected to evaluate prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count (PLT), blood lactic acid (Lac), thrombomodulin (TM), thrombin sensitive protein-1(TSP-1), von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1). Pathological changes were examined in the liver, kidney, lung, intestine, and heart. Results When the core temperature reached 42 ℃, the running distance and running time of rats in the Shengmaiyin group were significantly longer than those in the heatstroke group [(456.3±92.3) m vs.282.8±87.5) m, P<0.05; (36.3±6.3) min vs. (21.7±7.0) min, P<0.05]. Compared with the control group, PT and APTT in the heatstroke group were significantly prolonged [(13.8±0.7) s vs. (9.9±0.7) s, P<0.05; 78.3(36.0, 120.0) s vs. 19.0(16.6, 22.5) s,P<0.05], Lac was significantly increased [(10.5±2.0) mmol/L vs. (4.0±0.7) mmol/L, P<0.05], and PLT decreased significantly[(590.3±80.2)×10⁹/L vs. (1750.3±283.0)×10⁹/L, P<0.05], plasma TM, vWF, TSP-1, and PAI-1 levels increased significantly[2.1(1.8, 2.7) ng/ml vs. 1.6(1.5±1.7) ng/ml, P<0.05; (953.1±60.0) pg/ml vs. (462.3±37.0) pg/ml, P<0.05; (78.1±19.8) ng/ml vs. (59.3±12.0) ng/ml, P<0.05; (1945.7±74.5) ng/ml vs. (1487.6±259.1) ng/ml, P<0.05]. Compared with the rats in heatstroke group, the APTT of the rats in Shengmaiyin group was significantly shortened [36.6(31.1, 46.1) s vs. 78.3(36.0, 120.0) s, P<0.05], and the PLT elevated significantly [(980.5±302.4)×10⁹/L vs. (590.3±80.2)×10⁹/L, P<0.05], plasma TM, vWF and PAI-1 levels were significantly reduced [1.7(1.6, 1.8) ng/ml vs. 2.1(1.8, 2.7) ng/ml, P<0.05; (701.6±32.0) pg/ml vs. (953.1±60.0) pg/ml,P<0.05; (1582.8±71.6) ng/ml vs. (1945.7±74.5) ng/ml, P<0.05]. Thrombosis was found in liver, kidney, lung, intestine, and heart in heat stroke group, while no appreciable thrombosis was observed in Shengmaiyin group. Conclusion Shengmaiyin can relieve vascular endothelial cell injury, reduce consumption of coagulation factors and platelets, and prevent coagulation dysfunction in rats with EHS.