Objective:The study aimed to investigate the effects of exercise on the expression of ferroptosis-related proteins and the associated mechanisms in a post-traumatic stress disorder(PTSD)model induced by transient foot shock.Methods:Thirty-five male C57BL/6J mice(8 weeks old)were randomly divided into three groups:Control group,PTSD group,and Exe+PTSD group.PTSD model mice were established by foot-shock and PTSD behaviors were assessed using a fear conditioning box.Iron distribution areas were detected by Fe3+staining.Western Blot analysis were performed to determine the expression level of ferroptosis-related proteins in the mice.Results:Compared to the control group,the freezing time and Fe3+distribution areas in the cortex and hippocampus were significantly increased in the mice with PTSD(P＜0.05).The levels of ferroportin1(FPN1),glutathione peroxidase 4(GPX4),and brain-derived neurotrophic factor(BDNF)proteins were significantly decreased(P＜0.05),while the expression of high mobility group box 1(HMGB1)protein was significantly elevated(P＜0.05).Exercise significantly reduced freezing time and Fe3+accumulation in the cortex and hippocampus(P＜0.05),and it also up-regulated the expression of FPN1,GPX4,and BDNF proteins(P＜0.05),while down-regulating HMGB1 expression compared to the PTSD group(P＜0.05).Conclusion:This study demonstrates that PTSD induces the ferroptosis-related pathway in mice,and exercise can inhibit iron accumulation and reverse the expression of ferroptosis-related proteins induced by PTSD,there-by alleviating PTSD-like behavior in mice.