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Background: Depression commonly co-occurs with inflammatory bowel disease (IBD). Abnormal glutamate levels in the insula and altered plasma inflammatory biomarkers are observed in IBD and depression. However, the changes in glutamate concentrations in insular subregions in IBD and their relationship with depression and inflammatory markers remain unclear. This study aimed to investigate differences in glutamate concentrations in insular subregions between IBD patients and healthy controls (HCs) and their correlation with depression scores and inflammatory markers. Methods: Forty-two IBD patients (19 active, IBD-A; 23 in remission, IBD-R) and 46 HCs underwent glutamate chemical exchange saturation transfer (GluCEST) magnetic resonance imaging. Blood samples from 37 IBD patients were collected for plasma inflammatory biomarker analysis. GluCEST indices in insular subregions were measured. The Hospital Anxiety and Depression Scale (HADS-D) was used to estimate depression symptoms. Whole-brain voxel-based analysis using one-way ANOVA explored between-group differences in GluCEST indices within the insula. FDR-corrected partial correlation analysis evaluated the relationships between GluCEST, depression symptoms, and inflammatory factors. Results: GluCEST indices decreased in IBD patients in the left dorsal dysgranular subregion of the insula (dId) (uncorrected p