Serum β-glucuronidase activity has been determined by the new, specific method of Fishman in 100 patients with diabetes mellitus. The enzyme activity was increased significantly as compared with suitable controls—a mean value of 2,160 units for the diabetics vs 1,260 for the controls. It was not related to the intensity of hyperglycemia or the requirement for insulin. It is believed that the increased activity of β-glucuronidase can be explained by the operation of a noninsulin-sensitive pathway for glucose metabolism such as the glucuronic acid cycle. This pathway is known to become more active in diabetes. It is speculated that acceleration of the glucuronic acid cycle stimulates the synthesis of mucopolysaccharides and glycoproteins, and this induces greater β-glucuronidase activity to reduce their concentration.