A case of newly diagnosed non-insulin-dependent diabetes mellitus with immediate-type allergy against semisynthetic human insulin is reported. She experienced immediate-type allergy 2 months after initial insulin treatment. A skin test showed that she had allergy against the insulin itself but not the additives. The amino acid sequence of the semisynthetic human insulin was identical to that of endogenous native insulin and, moreover, the patient had not been treated with animal-derived insulin previously, so a structural change to the semisynthetic formulation at the injected subcutaneous site might have antigenicity. An H<sub>1 </sub>histamine blocker markedly diminished the skin reaction to insulin, and her plasma glucose and glycosylated hemoglobin A<sub>Ic</sub> became well controlled. In summary, we experienced a diabetic patient with human insulin allergy at the time of initial insulin treatment, emphasizing that the possibility of human insulin allergy should be considered whenever a patient is started on insulin therapy.