Background. Adjustable gastric banding (AGB) is the most common procedure performed for severe obesity; however, the physiological mechanisms by which it causes weight loss remain poorly understood. We have recently developed a rat model of Roux-en-Y gastric bypass (RYGB) that leads to 20% weight loss in diet-induced obese Sprague-Dawley (DIO-SD) rats. Postoperative weight loss is associated with decreased food intake, thermogenesis, increased energy expenditure, and a decrease in circulating ghrelin levels, suggesting that RYGB alters central weight regulatory mechanisms at multiple levels. To examine the mechanisms of weight loss after AGB, we sought to develop a rat model that could be examined in parallel with the rat model of RYGB. Methods. We designed an adjustable gastric band that fits rat esophageal/gastric anatomy to develop a model that closely resembles the human operation. The band is placed circumferentially around the rat stomach and is attached to a subcutaneously-implanted injection port. AGB-treated rats underwent postoperative band adjustments twice weekly with saline injection/withdrawal as needed, based on postoperative food intake and body weights. We compared 3 groups of DIO-SD rats that were matched for age and weight: an AGB-treated group, a RYGB-treated group, and a sham-operated (laparotomy) control group (SO). Results. After AGB, RYGB, or sham surgery, rats exhibited normal grooming, eating and social behaviors. Four weeks after surgery, AGB and RYGB-treated rats weighed 9.8% and 19% less than SO animals, respectively (p≤ 0.04 for both; Figure). At this time, AGB and RYGB-treated rats consumed 9.3% and 17.4% less food than controls, respectively. In contrast to the decreased circulating ghrelin levels seen after RYGB in rats, AGB-induced weight loss was associated with a 13% increase in plasma ghrelin. Conclusions. We have developed a novel, durable, and clinically relevant rat model of AGB that induces sustained weight loss without apparent ill effects. This model will facilitate studies to determine the physiological and molecular basis of weight loss after AGB. Analysis of the effect of surgery on circulating ghrelin suggests fundamental differences in the mechanisms by which AGB and RYGB cause weight loss. More detailed understanding of these differences could help guide the surgical approach to patients with obesity and facilitate the development of novel therapies with similar benefits and lower associated risks.