Type 1 diabetes is characterized by a mononuclear infiltration, commonly called «insulitis». The cells that constitute the insulitis are mainly monocytes that are recruited from extraislet areas and arrive at the islet site via the vascular system. Infiltrating cells must then pass across the endothelia to gain access to the islet parenchyma. The anatomy and physiology of the islet microvasculature shows that islet B cells are firstly perfused and influence both endocrine non-B islet cells and periinsular exocrine cells. The low dose streptozocin (LDS) treatment is able to induce, other than a monocyte/macrophage recruitment and activation, islet vascular alterations, mainly at the leve1 of post-capillary venules encircling the islets of Langerhans and a concomitant fa11 in Superoxidedismutase (SOD) (the first cellular defence against free radicals) activity. These findings, together with the increase in vascular permeability and the morphological evidence of areas of oedema formation within the islets, have raised the interest in the «microvasculm> approach to this disease. Actually the reduction in B-cell perfusion and the concomitant attack by phagocytes with a fall in SOD activity should be considered as events that are linked to each other. On the other hand both macrophages and endothelia are able to produce free radicals and, in particular, nitric oxide. This confirms that the islet vascular system seems to be involved in early insulitis and B-cell lysis.