Adiponectin, an adipose-specific protein hormone, is secreted from white adipose tissue and involved in glucose and lipid metabolism. It is assembled into low-molecular-weight trimer (LMW), middle molecular-weight hexameric (MMW) and high-molecular-weight (HMW), among which HMW exhibits higher activity. In this study, we proved that C-reactive protein (CRP), an inflammatory marker, inhibited adiponectin expression, especially HMW in time-and dose-dependent manners. Furthermore, CRP decreased the HMW/total adiponectin ration and reduced adiponectin assembly by increasing ERp44, and decreasing Ero1-alpha and DsbA-L. CRP activated pAkt, the downstream of PI3K. Inhibition of PI3K or pAkt abolished the effect of CRP. Our study suggested that CRP decreased adiponectin expression and multimerization, while CRP-induced decline in adiponectin might be mediated through the PI3K/Akt pathway. (C) 2016 Elsevier Inc. All rights reserved.