While immunologic responses to insulin such as cutaneous reactivity and antibody against insulin are common significant clinical problems related to those immunologic reactions are uncommon. Immunologic responses that have been described included Gell and Coombs type I, II, and IV. The antigen may be the result of any of several factors: insulin as a heterologous protein, altered tertiary structure of insulin, presence of non-insulin protein contaminants, or pharmaceutical formulation additives. IgE mediated local reactions are the most common and almost always subside spontaneously. IgE mediated anaphylaxis is the most important immunologic problem; it can be managed safely and successfully by temporary reduction in dose or by insulin desensitization. Other systemic immunologic reactions, insulin resistance and serum sickness, are extremely rare and respond to corticosteroid therapy.