The impact of a six month body weight supported treadmill (BWST) training program on glucose homeostasis and muscle metabolic characteristics was investigated. Nine individuals (31±3 yr, 8.1±2.5 yr post-injury; means±SE) with incomplete spinal cord injury (SCI) trained three times weekly for a total of six months. Training session duration and intensity (velocity) increased by 54±10% (P<0.01) and 135±20%, respectively. Muscle biopsies and a modified glucose tolerance test (100g glucose with [U-¹³C]glucose) were performed before (PRE) and after training (POST). Training resulted in a reduction in area under the curve (AUC) of glucose x time (-15±4%) and insulin x time (-33±8%; both P<0.05). Oxidation of exogenous (ingested) glucose increased as a result of training (PRE = 4.4±0.7 g/h, POST = 7.4±0.6g/h; P<0.05), as did oxidation of endogenous (liver) glucose (PRE = 3.8±0.3 g/h, POST = 5.2±0.3 g/h; P<0.05). Training resulted in increased muscle glycogen (80±23%; P<0.05) and GLUT-4 content, and hexokinase II enzyme activity (126±34% and 49±4%, respectively, both P<0.01). Resting muscle PCr content also increased following training (PRE = 62.1±4.3, POST = 78.7±3.8, both mmol/kg dry weight and P<0.05). Six months of thrice weekly BWST training in persons with an incomplete spinal cord injury improved blood glucose regulation by increasing oxidation and storage of an oral glucose load. Increases in the capacity for transport, and phosphorylation glucose in skeletal muscle are likely playing a role in these adaptations.