The small intestine of obese animals supplies nutrients to a metabolic live mass (body weight 0.75) that is much higher than that of age- and sex-matched lean animals. To determine the mechanisms of adaptation of the small intestine to obesity, we determined the rate of uptake of D-glucose and five amino acids, the site density of intestinal D-glucose transporters, and the permeability of the absorptive mucosa in isolated everted intestinal sleeves of genetically obese male mice (C57BL/6J ob/ob) and their lean male littermates. Intestinal D-glucose, proline, alanine, aspartate, leucine, and lysine uptakes per milligram were each similar in the small intestine of obese and control mice. Mucosal permeability, site density of intestinal D-glucose transporters, and their affinity for phlorizin were also each similar between obese mice and their lean controls. In contrast, intestinal D-glucose, proline, alanine, aspartate, leucine, and lysine uptakes per centimeter of small intestine were each approximately 40% greater in obese mice compared with lean controls (P < 0.001 to P < 0.08, depending on the nutrient and intestinal region). Differences in total absorptive capacity for any nutrient between the small intestine of obese and lean mice reflect mainly differences in intestinal weights. Thus, genetic obesity is associated with increased intestinal growth, which augments absorption of all types of nutrients. The ratio of intestinal absorptive capacity to metabolic mass, and of intestinal mass to metabolic mass, does not change with obesity, indicating that in mice, changes in intestinal mass and in absorptive capacity are directly proportional to changes in metabolic mass.