We investigated the effect of subdiaphragmatic vagal deafferentation (SDA) on food intake, body weight gain, and metabolism in obese and lean Zucker rats. Prior to and after recovery from surgery, food intake and body weight gain were recorded, and plasma glucose and insulin were measured in tail-prick blood samples. After implantation of a jugular vein catheter, an IVGTT was performed followed by minimal modeling to estimate the insulin sensitivity index. Food intake relative to metabolic body weight (g/kg^0.75) and daily body weight gain after surgery were lower in SDA obese than in SHAM obese Zucker rats (Food intake SHAM: 67.5 ± 1.2, SDA: 60.8 ± 1.1 g/kg^0.75, mean ± SE, p < 0.05; Body weight gain SHAM: 6.1 ± 0.2, SDA, 5.1 ± 0.3 g, mean ± SE, p < 0.01), but not in lean (Food intake SHAM: 55.1 ± 0.8, SDA: 53.4 ± 1.0 g/kg^0.75, ns; Body weight gain SHAM, 2.9 ± 0.2, SDA, 3.2 ± 0.2, ns) rats. Prior to surgery, plasma glucose and insulin concentrations were lower in lean than in obese rats, but did not differ between surgical groups within both genotypes. Four weeks after surgery, plasma glucose (SHAM, 6.9 ± 0.2, SDA, 6.7 ± 0.1 mmol/L, ns) and insulin (SHAM, 1.3 ± 0.2, SDA, 1.2 ± 0.2 ng/ml, ns) were still similar in SDA and SHAM lean rats, but significantly lower in SDA than in SHAM obese rats (glucose: SHAM, 8.3 ± 0.2, SDA, 7.2 ± 0.3, p < 0.05; insulin: SHAM, 13.5 ± 1.4, SDA, 10.4 ± 0.6, p < 0.01). The IVGTT revealed a significant downward shift of the plasma insulin profile by SDA in obese, but not in lean animals, while the plasma glucose profile was not affected. SDA decreased the area under the curve for insulin, but not glucose, in obese Zucker rats. The insulin sensitivity index was higher in lean than in obese rats, but was not affected by SDA in both genotypes (lean: SHAM, 6.24 ± 1.53, SDA, 7.06 ± 1.19, ns; obese: SHAM, 1.54 ± 0.22, SDA, 1.73 ± 0.30, ns). These results suggest that the elimination of vagal afferent signals from the upper gut reduces food intake and body weight gain without affecting the insulin sensitivity index measured by minimal modeling in Zucker obese rats.