Studies of adipogenic protein induction have led to a new appreciation of adipose tissue’s role as an endocrine organ. Adipocyte-derived “adipokines” such as adiponectin, leptin, and vaspin (visceral adipose tissue-derived serine protease inhibitor) exert hormone-like activities at the systemic level. In this study, we examined the secretome of primary cultures of human subcutaneous adipose-derived stem cells (ASCs) as an in vitro model of adipogenesis. Conditioned media obtained from four individual female donors after culture in uninduced or adipogenic induced conditions was compared by 2-dimensional gel electrophoresis and tandem mass spectroscopy. Over 80 individual protein features showing =2-fold relative differences were examined. Approximately 50% of the identified proteins have been previously described in the secretome of murine 3T3-L1 pre-adipocytes or in the interstitial fluid derived from human mammary gland adipose tissue. As reported by others, we found that the secretome included proteins such as actin and lactate dehydrogenase, that do not display a leader sequence or transmembrane domain and are classified as “cytoplasmic” in origin. Moreover, we detected a number of established adipokines, such as adiponectin and plasminogen activator inhibitor 1 (PAI-1). Of particular interest was the presence of multiple serine protease inhibitor proteins (serpins). In addition to PAI-1, these included pigmented epidermal derived factor (PEDF, confirmed by western immunoblot), placental thrombin inhibitor, pregnancy zone protein, and protease C1 inhibitor (C1 inh). These findings, together with the recent identification of vaspin, suggest that the serpin protein family warrants further proteomic investigation with respect to the etiology of obesity and type 2 diabetes.