The Movement of the interstitial fluid in extracellular matrices not only affects the mechanical properties of soft tissues, but also facilitates the transport of nutrients and the removal of waste products. In this study, we aim to quantify interstitial fluid movement and fluid-matrix interaction in a new loading configuration—confined tissue indentation, using a poroelastic theory. The tissue sample sits in a cylindrical chamber and loading is applied on the top central surface of the specimen by a porous indenter that is fixed on the specimen. The interaction between the solid and the fluid is examined using a finite element method under ramp and cyclic loads. Typical compression-relaxation responses of the specimen are observed in a ramp load. Under a cyclic load, the system reaches a dynamic equilibrium after a number of loading cycles. Fluid circulation, with opposite directions in the loading and unloading phases in the extracellular matrix, is observed. The most significant variation in the fluid pressure locates just beneath the indenter. Fluid pressurization arrives at equilibrium much faster than the solid matrix deformation. As the loading frequency increases, the location of the peak pressure oscillation moves closer to the indenter and the magnitude of the pressure oscillation increases. Concomitantly, the axial stress variation of the solid matrix is reduced. It is found that interstitial fluid movement helps to alleviate severe strain of the solid matrix beneath the indenter. This study quantifies the interaction between the interstitial fluid and the extracellular matrix by decomposing the loading response of the specimen into the “transient” and “dynamic equilibrium” phases. Confined indentation in this manuscript gives a better representation of some in vitro and in vivo loading configurations where the indenter covers part of the top surface of the tissue.