: Lipodystrophies is a really rare group of diseases characterized by altered body fat amount and/or repartition and serious insulin resistance.We reported a lean Chinese girl with acquired generalized lipodystrophy, who had a long history of poorly controlled diabetes mellitus (DM) despite with extremely high dose insulin (6 u/kg/d) therapy, combined with severe hypertriglyceridemia and acanthosis nigricans. The differential diagnosis of Lipodystrophies should be considered in lean patients presenting with early onset DM, combined with serious insulin resistance.