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Abstract: Introduction: Despite the occurrence of a severe allergic reaction including an anaphylactic shock, a drug may remain essential and impossible to replace. This may be the case of insulin in a diabetic patient. We describe the case of an anaphylactic shock to human insulin in whom a desensitization protocol was successfully achieved. Case report: A 50-year-old type 2 diabetic man presented one year after initiation of the insulin therapy an anaphylactic shock following the subcutaneous administration of a human insulin containing protamine (Insulatard®). A desensitization protocol to human insulin was performed and allowed to use two human insulin analogues containing no protamine (asparte and glargine), with a two-year event-free follow-up. Positive skin tests with insulin and protamine, and the presence of insulin specific IgE were evidenced of an IgE-mediated mechanism. Desensitization was monitored by skin tests, Maunsell''s test, measurement of specific IgE and IgG4, and the basophil activation test. The decrease of basophil sensitivity to insulin is an early marker for tolerance induction. Conclusion: The effectiveness of the desensitization to human insulin underlines the importance to define the modalities of such desensitization protocol and of the monitoring of the tolerance induction. [Copyright &y& Elsevier]