Proinflammatory conditions, within a variety of biological contexts, are linked with an increased risk for developing depression, yet the neurobiological substrates that drive this immune-brain interaction are difficult to isolate in the clinic and remain poorly understood.Using rodent models, we can begin to tease apart the molecular pathways and neural circuits that are involved in precipitating inflammation-induced depression-like behavior.Numerous groups have demonstrated the critical role that proinflammatory cytokines play in mediating the hosts behavioral response to immune challenge, and over the past several years, their critical role has been expanded to include behaviors that may reflect a depression-like behavioral state.While anti-inflammatory treatments are being explored as novel antidepressant therapy, the kynurenine pathway of tryptophan metabolism has emerged as a promising new target for treating inflammation-induced depression.We demonstrated that immune challenge increases the kynurenine:tryptophan ratio and alters the expression profile of kynurenine pathway enzymes within the brain.Inhibition of indoleamine 2,3-dioxygenase (IDO) largely attenuated the occurrence of depression-like behaviors in response to the proinflammatory stimuli, while acute administration of L-kynurenine increased depression-like behavior.Together, these data suggest that the kynurenine pathway may provide novel therapeutic targets for improving treatment of inflammation-related depression.