A 40-year-old Japanese male with diabetic scleredema was reported. Histochemical examination revealed that the alcian blue and colloidal iron strains were positive in the dermis, especially in the lower dermis. The biochemical analyses of the 3 horizontally sliced layers of scleredema skin revealed that (1) glycosaminoglycan content was low in the upper and middle dermis, which was chiefly due to the decrease in hyaluronic acid, (2) dermatan sulfate content was constant among the 3 layers, (3) the content of collagen in the upper and middle dermis was higher, and (4) the ratio of type I/type III collagen in the whole involved skin was normal. From these results, we speculate that the increase in collagen content in the upper and middle dermis may be essential for the pathophysiology of the disease.