ABSTRACT.Purpose: To more fully investigate the effect of hyperglycemia on the aerobic metabolism of the corneal epithelium. Methods: Corneal epithelial oxygen uptake rates and adenosine triphosphatase (ATPase) activities were measured in alloxan-induced diabetic and control rabbits over a 10 week period. Results: A transient reduction in epithelial oxygen uptake rate was seen at week 1. A chronic 14% reduction in oxygen consumption occurred after 6 weeks of hyperglycemia. Epithelial ouabain-sensitive ATPase activity was unaffected by 10 weeks of hyperglycemia. Epithelial ouabain-insensitive ATPase activity decreased 14% after 10 weeks of hyperglycemia. Conclusions: Ten weeks of hyperglycemia in the alloxan induced diabetic rabbit was associated with a 14% decrease in corneal oxygen uptake, a 14% decrease in corneal epithelial ouabain-insensitive ATPase activity and no change in corneal epithelial ouabain-sensitive ATPase activity. The Crabtree effect may help explain some of the clinical signs seen in the diabetic cornea as well as explaining why diabetic patients can wear contact lenses with minimal clinical problems.