The secretory granules of the β-cells (β-granules) in the pancreatic islets differ in shape in different animals. Whether β-granules are made entirely of insulin or not is unknown. Ten mixed-breed dogs were used and separated into two groups. One was a control group and the other served as those with experimental diabetes mellitus (DM) and received injections of Streptozotocin. After the injections, blood glucose was checked on day 14. The pancreas was removed after fixation by perfusion and post-fixed with Caulfield’s fixative. The specimens were then processed and observed under an transmission electron microscope (TEM). Immunocytochemistry using antibodies to insulin was also performed. The β-cells in the DM animals were reduced in size and displayed fewer electron dense granules. Additionally, almost all of the cell organelles had decreased in number Immunocytochemical observations of the control β-cells showed a strong positive reaction on the rodshaped and spherical granules. The number of rodshaped granules in control dogs ranged from 3299 to 3559, while in DM animals they varied from 374 to 602. The spherical granules in the controls numbered between 168 and 295 as compared to the DM dogs which ranged from 394 to 706 in each animal. The ratio of rodshaped and spherical granules in the controls was 5:1 and in the DM dogs 1:1. It was understood that the diminution in the total number of granules in the DM dogs was mainly due to a decrease of rodshaped granules. It is assumed that the rodshaped granule corresponded to proinsulin, the storage form of the insulin, and the spherical granules to the active form of insulin. However, there have been no reports discussing this relationship. The present study demonstrated that the βgranules, especially rodshaped granules decreased in DM animals, whereas the percentage of spherical granules remained the same or were even elevated compared to the normal, controls. Thus, it is believed that Streptozotocin mainly attacked the pathway where preproinsulin is converted to proinsulin.