Although human insulin is widely used, insulin allergy is still an important issue. Desensitization is one of the strategies to overcome insulin allergy, but there are few report concerning the mechanism of immune tolerance to insulin achieved by desensitization. Based on the previous studies regarding immunotherapy, it can be understood that changes in allergen specific antibody may be a probable mechanism. We report time-serial changes in insulin-specific antibodies after successful desensitization of type I hypersensitivity to insulin. A 68-year-old man visited our clinic due to dyspnea, loss of consciousness and whole body rash with erythema immediately after the injection of human insulin. The patients showed positive skin reactions to all available human insulins. Enzyme linked immunosorbent assay (ELISA) demonstrated that human insulin specific IgE level increased. We injected human insulin (aspart) to patient subcutaneously with gradual increase manners and finally achieved successful insulin desensitization without serious systemic reactions. Human insulin-specific antibody was measured 4, 8 and 12 weeks after desensitization, which showed interesting time-serial changes; specific IgE gradually decreased, while IgG1, IgG2 and IgG4 gradually increased.