Mesenchymal stem cells (MSCs) are capable of modulating the immune system and have been used to successfully treat a variety of inflammatory diseases in preclinical studies. Recent evidence has implicated paracrine signaling as the predominant mechanism of MSC therapeutic activity. We have shown in models of inflammatory organ failure that the factors secreted by MSCs are capable of enhancing survival, downregulating inflammation, and promoting endogenous repair programs that lead to the reversal of these diseases. As a marker of disease resolution, we have observed an increase in serum IL-10 when MSC-conditioned medium (MSC-CM) or lysate (MSC-Ly) is administered in vivo. Here we present an in vitro model of IL-10 release from blood cells that recapitulates this in vivo phenomenon. This assay provides a powerful tool in analyzing the potency of MSC-CM and MSC-Ly, as well as characterizing the interaction between MSC-CM and target cells in the blood.