Objective:Cerebral ischemia reperfusion injury(CIRI)can cause damage to distant organs,such as the gastrointestinal tract,through the gut-brain axis.Melatonin is known to play a neuroprotective role by activating specific receptor pathways.However,the changes of melatonin receptors in the gastrointestinal tract after brain injury and their relationship with intestinal injury are still unclear.Methods:Twenty-four male Sprague-Dawley rats were randomly di-vided into the Sham group and CIRI group.The CIRI model was prepared by Zea-Longa method.The jejunum,ileum,and colon tissues of the rats were collected 2 h after ischemia and 24 h after reperfusion.The damage of intestinal and brain tissues was observed by using 2,3,5-triphenyl tetrazolium chloride(TTC)and HE staining.The positive expres-sion of zonula occludens-1(ZO-1)and Claudin5 was observed by immunofluorescence staining.The melatonin receptor 1(MT1)and melatonin receptor 2(MT2)expression was detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR),immunofluorescence staining and Western Blot.The correlation between the melatonin receptors and intestinal tight junction proteins was analyzed by general linear regression.Results:TTC staining showed that the infarct size of rats in the CIRI group was significantly higher than that in the Sham group.HE staining showed that intestinal villi was broken and shortened,and goblet cells were reduced in the CIRI group.The results of immuno-fluorescence staining revealed that the positive expression of ZO-1 and Claudin5 in the intestinal tissues of rats in the CIRI group was significantly lower than that in the Sham group(P＜0.05).Compared with the Sham group,the RT-qPCR revealed a significantly lower expression of MT1 and MT2 mRNA in the CIRI group(P＜0.05),and the decrease in colon tissue was the most obvious.The results of immunofluorescence staining and WB also showed that the expression of MTl and MT2 in the CIRI group was significantly lower than that in the Sham group(P＜0.05).A gen-eral linear regression analysis revealed the difference in mean fluorescence intensities of MT1+and MT2+between the Sham group and the CIRI group were positively correlated with the difference of ZO-1+and Claudin5+between the two groups.Conclusion:After CIRI,the expression of both MT1 and MT2 receptors in various intestinal segments was de-creased,and the decrease in colon tissue was the most significant.It is suggested that the poor recovery of stroke may be related to the decrease of melatonin receptor.