A mechanical model was developed to study the indentation of an atomic force microscopic (AFM) tip on a cell with adhesion mediated by receptor-ligand binding. The effects of indentation rate, indentation depth, indenter size, and the mechanical properties of cells on the adhesion force were investigated. It was found that the presence of adhesion between the cell and AFM tip may affect both the loading curve and unloading curve, which may in turn change the extracted elastic modulus values using the conventional indentation models. It was found that an increase in the receptor-ligand reaction rate may lead to a transition from a decrease of the maximum adhesion force with the indentation rate to an increase of the maximum adhesion force with the indentation rate. It was also found that factors such as indenter size, indentation depth, and cell mechanical properties influence the maximum adhesion force, and their corresponding underlying mechanisms were discussed.