OBJECTIVE: Obesity and type 2 diabetes mellitus (T2DM) are associated with altered food-related neuronal functions. Besides weight loss, substantial improvement of glucose metabolism in patients with T2DM can be achieved by bariatric surgery. We aimed to target the neuronal and behavioral correlates of improved glycemic control after bariatric surgery. RESEARCH DESIGN AND METHODS: Two patient groups with T2DM were recruited. The treatment group (n = 12) included patients after Roux-en-Y gastric bypass (RYGB) surgery and a control group of patients who did not undergo surgery (n = 12). The groups were matched for age and current BMI. HbA1c was matched by using the presurgical HbA1c of the RYGB group and the current HbA1c of the nonsurgical group. Neuronal activation during a food reward task was measured using functional MRI (fMRI). Behavioral data were assessed through questionnaires. RESULTS: RYGB improved HbA1c from 7.07 ± 0.50 to 5.70 ± 0.16% (P < 0.05) and BMI from 52.21 ± 1.90 to 35.71 ± 0.84 kg/m(2) (P < 0.001). Behavioral results showed lower wanting and liking scores as well as lower eating behavior-related pathologies for the patients after RYGB than for similar obese subjects without surgery but impaired glycemic control. The fMRI analysis showed higher activation for the nonsurgical group in areas associated with inhibition and reward as well as in the precuneus, a major connectivity hub in the brain. By contrast, patients after RYGB showed higher activation in the visual, motor, cognitive control, memory, and gustatory regions. CONCLUSIONS: In obese patients with diabetes, RYGB normalizes glycemic control and leads to food reward-related brain activation patterns that are different from obese patients with less-well-controlled T2DM and without bariatric surgery. The differences in food reward processing might be one factor in determining the outcome of bariatric surgery in patients with T2DM.