1. 1. The effect of proximal and distal small bowel resection on intestinal glucose metabolism was studied in the rat. In a particle-free supernatant solution prepared from the mucosa of control animals, the specific activities of the following soluble enzymes were significantly greater in proximal mucosa: glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, fructokinase, and phosphofructokinase. Recovery of a soluble fraction of the particulate-bound enzyme, hexokinase, was greater from the distal mucosa. 3 and 7 months after proximal or distal resection, there was a significant increase in the specific activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrgenase in the mucosa of the remaining segments. No change was found for the other enzymes. 2. 2. Glucose utilization by normal proximal mucosa was six times greater than distal mucosa and did not change after intestinal resection. The percent of glucose metabolized by the pentose phosphate pathway was 5.3 ± 0.29 in normal proximal mucosa compared with 13.1 ± 1.15 in normal distal mucosa ( P < 0.001),. After distal or proximal small bowel resection, glucose metabolism via the pentose phosphate pathway increased to 8.4 ± 0.70% in the proximal remnant ( P < 0.005) and to 26.2 ± 4.97% in the distal remnant ( P < 0.025). The results indicate that an increase in the pentose phosphate pathway is part of the intestinal adaptation to small bowel resection. The relationship of this pathway to increased nucleic acid synthesis after resection is discussed.