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Background Depression is a major psychiatric comorbid condition of type 2 diabetes mellitus (T2DM). Serotonin, the major neurotransmitter implicated in depression, is a tryptophan derivative. Tryptophan is chiefly metabolised through the kynurenine pathway with indolamine-2,3-dioxygenase (IDO) as the rate-limiting enzyme. Hence, serum tryptophan and kynurenine concentrations and their ratio (K/T ratio) as a measure of IDO activity are possible biomarkers of depression in T2DM. Methods Severity of depression in adults with T2DM attending a primary care facility in Delhi was rated using the Hamilton Depression Rating Scale (HAM-D 17 items). Baseline serum tryptophan and kynurenine concentrations, along with their ratio, were estimated. A follow-up HAM-D rating was done after 16 weeks of standard therapy and the quantum HAM-D score improvement was correlated with the K/T ratio. Results Of 106 people with T2DM screened for depression, 52 had syndromal depression and were recruited for the study. There was no significant association between age, sex, marital status, religion, serum tryptophan, and kynurenine levels with respect to the severity of depression, but the mean K/T ratio was significantly higher among those with severe depression (p<0.05). There was a significant correlation between serum kynurenine and HAM-D score improvement at 16 weeks. Conclusion K/T ratio, a measure of IDO activity, was found to be a severity marker for depression in T2DM, without any prognostic significance. Further studies are required to explore the K/T ratio as a state marker, severity marker, and prognostic biomarker of depression in people with T2DM.