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Ghrelin, a brain-gut peptide that induces anxiety and other abnormal emotions, contributes to the effects of insomnia on emotional behavior. In contrast, the traditional Chinese Medi-cine remedy Wen Dan Tang reduces insomnia-related anxiety, which may perhaps correspond to changes in the brain-gut axis. This suggests a possible relationship between Wen Dan Tang’s pharmacological mechanism and the brain-gut axis. Based on this hypothesis, a sleep-deprived rat model was induced and Wen Dan Tang was administered using oral gavage during model es-tablishment. Wen Dan Tang signiifcantly reduced insomnia-related anxiety and prevented Ghrelin level decreases following sleep deprivation, especially in the hypothalamus. Increased expression of Ghrelin receptor mRNA in the hypothalamus was also observed, suggesting that reduced anxi-ety may be a result of Wen Dan Tang’s regulation of Ghrelin-Ghrelin receptors.