The docking and fusion of membrane-bound vesicles at the cell plasma membrane are brought about by several participating vesicle membrane, plasma membrane, and soluble cytosolic proteins. An understanding of the interactions between these participating proteins will provide an estimate of the potency and efficacy of secretory vesicle docking and fusion at the plasma membrane in cells of a given tissue. Earlier studies suggest that in chronic pancreatitis, glucose intolerance may be associated with impaired exocytosis/endocytosis of hepatic insulin receptor and glucose transporter proteins. In this study, the binding force profiles between microsome membrane proteins and plasma membrane proteins in liver obtained from normal and pancreatitic rats have been examined using atomic force microscopy. The ability of a VAMP-specific antibody to alter binding between microsome- and plasma membrane-associated membrane proteins was examined. In pancreatitic livers, a significant loss in microsome-plasma membrane binding is observed. Furthermore, our study shows that, in contrast to control livers, the microsome-plasma membrane binding in pancreatitic livers is VAMP-independent, which suggests an absence of VAMP participation in membrane-microsome binding. In confirmation with our earlier findings, these studies suggest altered membrane recycling in liver of rats with chronic pancreatitis.