Signal transducer and activator of transcription 3 (STAT3) is abundantly expressed in the adipose tissue of obese mice and humans, but the role of STAT3 in adipogenesis is still not fully understood. In the present study, we discovered an activation of STAT3 during the early differentiation stage of mouse 3T3-L1 preadipocytes. Stat3 knockdown using siRNA blocked cell cycle progression of both preadipoctes and early differentiating cells. Moreover, accumulation of lipid droplets was inhibited by Stat3 knockdown. Importantly, in the nucleus of early differentiating cells, we demonstrated that STAT3 protein co localized with high-mobility-group protein AT-hook 2 (HMGA2), which was reported to promote adipogenesis in a previous study. Taken together, our data indicate that STAT3 and HMGA2 cooperatively promote adipogenesis which highlight a more detail understanding of STAT3 related transcription factor network during adipogenesis. (C) 2016 Elsevier Inc. All rights reserved.