Obesity has become a global health problem and it is linked to a higher risk of diseases and metabolic disorders such as diabetes, cardiovascular disease, and cancer. The adipose tissue plays an important role in monitoring and controlling whole-body metabolism by secreting a variety of bioactive molecules such as adiponectin. Deficiencies of this hormone can cause type It diabetes and cardiovascular disease both in mice and in humans. Therefore, adiponectin is an attractive molecule to use in human therapy, particularly in a recombinant form. The source of recombinant adiponectin could be the expression of full-length adiponectin either in Escherichia coli, or in baculovirus. In this work we express and purify human adiponectin in both systems. The adiponectin produced by baculovirus was found to be 10 times more active as far as oligomerization and human pre-adipocyte differentiation are concerned, when compared with adiponectin produced by E coli. We presume that adiponectin expressed in baculovirus has post-translation modifications not made by bacteria which may be responsible for these differences in activity. This renders adiponectin produced by baculovirus a better candidate for the treatment of type II diabetes and cardiovascular disease. (C) 2008 Elsevier Inc. All rights reserved.