The presence of insulin receptor antibodies is a rare cause of insulin resistance. Patients usually have a combination of hyperglycemia, insulin resistance, acanthosis nigricans, and autoimmune features. We report a patient with systemic lupus erythematosus and severe insulin resistance due to insulin receptor antibodies. The most striking aspect of the clinical presentation is the resistance to insulin therapy, with our patient unresponsive to doses of up to 154,075 units in a day. While on a low-dose glucocorticoid therapy, the patient had clinical improvement, and glucose levels subsequently became normal even without insulin and glucocorticoid.