Objective <p>To investigate the effects of simvastatin pretreatment on platelet activation and hypercoagulable state in septic mice.</p> Method <p>60 Sprague–Dawley (SD) mice were divided into three groups: healthy control (group A), sepsis (group B) and simvastatin intervention (group C). The sepsis model was established by intraperitoneal injection of lipopolysaccharide in the group B: the group A was injected with normal saline, and the group C was injected with 10&#xa0;μg/ml simvastatin 5&#xa0;ml of simvastatin for 3&#xa0;h. The changes of protein expression were detected by Western blot, blood coagulation indexes were analyzed, and the levels of serum platelet activating factor, thrombomodulin, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by enzyme linked immunosorbent assay (ELISA) detection kit.</p> Result <p>The levels of thrombomodulin and platelet activating factor in mice of the group B were significantly higher than those in the group A (<i>P</i> &lt; 0.05). The levels of thrombomodulin and platelet activating factor in the group C of mice were significantly lower than those in the group B (<i>P</i> &lt; 0.05), which were down-regulated by 20.44% and 33.33%, respectively (<i>P</i> &lt; 0.05). The PT and APTT times of mice in the group B were significantly lower than those in the group A (<i>P</i> &lt; 0.05). The PT and APTT times of mice in the group C were significantly higher than those in the group B (<i>P</i> &lt; 0.05), which were upregulated by 29.01% and 13.08%, respectively (<i>P</i> &lt; 0.05). The SOD level of mice in the group B was significantly lower than that in the group A, and the MDA level was significantly higher than that in the group A (<i>P</i> &lt; 0.05). The SOD level in the group C of mice was significantly higher than that in the group B, which was upregulated by 24.77%, and the MDA level was significantly lower than that in the group B, which was down-regulated by 22.96% (<i>P</i> &lt; 0.05). The levels of serum IL-6, TNF-α and IL-1β in mice of the group B were higher than those in the group A (<i>P</i> &lt; 0.05). The levels of serum IL-6, TNF-α and IL-1β in the group C of mice were lower than those in the group B by 45.97%, 28.72% and 16.59%, respectively (<i>P</i> &lt; 0.05). The expression levels of AMPK and UCP2 proteins in the group B of mice were lower than those in the group A (<i>P</i> &lt; 0.05). The expression levels of AMPK and UCP2 proteins in the group C of mice were higher than those in the group B, which were upregulated by 55.00% and 28.81%, respectively (<i>P</i> &lt; 0.05).</p> Conclusion <p>Simvastatin pretreatment can improve platelet activation and hypercoagulable state in septic mice.</p>