This study compares corneal thickness and corneal endothelial Na,K ATPase activity in normal and age-matched diabetic rabbits with up to 10 weeks of hyperglycemia. Corneal endothelial Na,K ATPase activity in normal rabbits increased between 10 and 20 weeks of age. Corneal thickness increased after 5 weeks of hyperglycemia. Decreased corneal endothelial homogenate Na,K ATPase activity was first seen after 10 weeks of hyperglycemia, though an earlier onset was possible due to sampling restrictions. Corneal endothelial homogenate Mg++ ATPase activity showed a transient increase after 2 to 5 weeks of hyperglycemia. This study shows that hyperglycemia in rabbit is associated with complex dynamic interactions between corneal thickness and corneal endothelial Mg++ ATPase and Na,K ATPase activities.