Type B insulin resistance syndrome is a rare disease that occurs due to the development of autoantibodies to the insulin receptor and can result in either severe insulin resistance and hyperglycemia or, conversely, hypoglycemia. Diabetes mellitus is often severe, usually transient, and poorly responsive to exogenous insulin. Diabetic ketoacidosis is an unusual consequence of this most severe form of transient diabetes mellitus.A 39-year-old Nigerian woman presented with significant weight loss, severe diabetic ketoacidosis, and severe insulin resistance requiring massive doses of exogenous insulin. She was diagnosed with systemic lupus erythematosus and type B insulin resistance syndrome. She was treated by immunomodulation with rituximab and pulse dose dexamethasone, and she entered euglycemic remission after 4 months of treatment. She remains independent of exogenous insulin 1 year later on maintenance azathioprine therapy.We report a case of severe type B insulin resistance syndrome complicated by severe diabetic ketoacidosis soon after the initial diagnosis of diabetes, despite large doses of exogenous insulin therapy. Our patient achieved euglycemic remission after combination immunomodulation. This case illustrates the severe catabolic state that may occur with high anti-insulin receptor antibody titers and that combination therapy with rituximab and dexamethasone, followed by maintenance azathioprine therapy for 1 year, is an effective treatment approach for the management of type B insulin resistance syndrome.