A 66-year-old woman suffering from pollinosis developed generalized urticaria after injection of intermediate-acting insulin for diabetes mellitus. She had human insulin-specific IgE, and in skin tests was positive for human recombinant insulin and negative for additives. Uniquely, she reacted to fast-acting and slow-acting insulin but not to long-acting insulin. We further confirmed that human insulin preparations could stimulate her peripheral basophils to release a significant amount of histamine. Genetically generated human insulin analogs, aspart and lispro, induced positive skin tests and histamine release from basophils. She was recommended to use a long-acting insulin preparation and was free from symptoms thereafter.