Abstract only Lack of compensatory vascularization causes hypoxia with adipose tissue dysfunction in obesity. Dysfunctional adipocytes instigate systemic low-grade inflammation which is associated with increased morbidity and mortality of metabolic disorders and related cardiovascular disease. A remaining challenge in the field is how to preserve adipocyte metabolic function by suppressing the negative aspect of inflammation, without blocking its angiogenic function. We investigated the role of IL-19, a uniquely immuno-modulatory, pro-angiogenic interleukin expressed also in adipose tissue. We hypothesize that IL-19 acts as a novel adipokine whose expression in expanding adipose depots is essential for maintaining glucose homeostasis. We report that IL-19 is expressed in adipose tissue at both the transcript and protein level and its expression is increased in inflamed visceral adipose tissue but not subcutaneous adipose tissue (p<0.05). Utilizing Il19 -/- knockout mice, we found the loss of IL-19 leads to a metabolic phenotype characterized by reduced glucose and insulin tolerance, increased adipose tissue hypoxia and fibrosis, decreased adipose tissue vessel density and increased adipocyte hypertrophy both in response to standard chow diet and chronic high fat diet (p<0.05). Acute treatment with IL-19 reduced glucose and insulin intolerance in obese wild-type mice (p<0.05). In primary murine epididymal adipocytes the addition of IL-19 leads to increased glucose uptake (p<0.05). These metabolic actions of IL-19 were linked to upregulation of the insulin type-2 receptor and subsequent increased expression/phosphorylation of the protein kinase B (Akt) in adipocytes. Overall, these data propose that IL-19 has novel therapeutic potential in that it can effectively allow adipose tissue expansion without concomitant inflammation and insulin insensitivity.