There is growing evidence that vagus nerve stimulation (VNS) exerts a suppressive effect on both short- and long-term feeding in animal models. We previously showed that VNS with high-frequency (10 Hz) electrical impulses decreased food intake and body weight in rats. In the present study, we investigated the effect of VNS with a low frequency (1 Hz) on the serum lipid concentrations, feeding behavior and appetite in rats fed a high-fat diet. The levels of appetite-regulating peptides were also assessed. Adult male Wistar rats were subcutaneously implanted with a microstimulator (MS) and fed a high-fat diet throughout the entire study period (42 days). The left vagus nerve was stimulated subdiaphragmatically by rectangular electrical pulses (10 ms, 200 mV, 1 Hz, 12 h a day) generated by the MS. The daily food intake and body weight were measured each morning. At the end of the experiments, the serum glucose, cholesterol, triglycerides, low-density lipoproteins, high-density lipoproteins, ghrelin, leptin and nesfatin-1 concentrations were measured. The adipose tissue content was evaluated by the assessment of the weight of the epididymal fat pads. Chronic VNS significantly decreased food intake, body weight gain and epididymal fat pad weight. VNS also lowered the total plasma cholesterol concentrations and triglyceride levels. Finally, the serum concentrations of nesfatin-1 were elevated, leptin levels were decreased, and ghrelin levels remained unchanged after VNS. The study demonstrates that chronic electrical VNS exerts anorexigenic effects, lowering the blood concentration of lipids. Increased nesfatin-1 levels may contribute to these effects.