Obesity is associated with increased fibrinogen production and fibrin formation which produces fibrin degradation products (FDP-E and FDP-D). Fibrin and FDP's both contribute to inflammation which would be expected to suppress glucose uptake and insulin signaling in adipose tissue, yet the effect of FDP-E and FDP-D on adipocyte function and glucose disposal is completely unknown. We tested the effects of FDP's on inflammation in 3T3-L1 adipocytes and primary macrophages and adipocyte glucose uptake in vitro. High-fat fed mice increased hepatic fibrinogen mRNA expression 9-fold over chow-fed mice with concomitant increases in plasma fibrinogen protein levels. Obese mice also displayed increased fibrinogen content of epididymal fat pads. We treated cultured 3T3-L1 adipocytes and primary macrophages with FDP-E, FDP-D, or fibrinogen degradation products (FgnDP-E). FDP-D and FgnDP-E had no effect on inflammation or glucose uptake. Cytokine mRNA expression in RAW264.7 macrophage-like cells and 3T3-L1 adipocytes treated with FDP-E induced inflammation with maximal effects at 100nM and 6 hours. Insulin stimulated ³H-2-deoxy-D-glucose uptake was reduced by 71% in adipocytes treated with FDP-E. FDP-E, but not FDP-D or FgnDP-E induces inflammation in macrophages and adipocytes and decreases glucose uptake in in vitro. FDP-E may contribute toward obesity associated acute inflammation and glucose intolerance although its chronic role in obesity remains to be elucidated.