By using biochemical and light-microscopical techniques, insulin-like growth factor-2 (IGF-2) has recently been found in adult pancreas, co-localized immunohistochemically with insulin in the islet B-cells. The purpose of this study was to trace IGF-2 immunoreactivity (IR) at the ultrastructural level in normal and diabetic Goto-Kakizaki (GK) rats. Using a pre-embed-ding technique and immuno-gold-silver staining, IGF-2 antibody binding was localized exclusively to the halo of a subset of secretory β-granules in normal rats. Insulin IR occurred more frequently in the granules. GK rats had, in addition to normal-looking islets, some islets with irregular shape and an increased amount of fibrous tissue, so-called “starfish-shaped” islets. In these, β-granules were usually found, but most of the B-cells were also occupied by large, usually electron-translucent vesicles, some resembling crinophagic bodies, i.e., the sign of intracellular degradation of secretory granules. In starfish-shaped islets, IGF-2 IR was localized to the halo of β-granules, as in GK islets with normal appearance. Occasionally, IGF-2 IR was also found in the cytoplasm and even in adjacent fibroblasts. Insulin IR was restricted to β-granules. Because the lysosomes have IGF-2 receptors, the presence of IGF-2 peptide in secretory granules could explain why some granules are guided to lysosomes for degradation.