We calculate the rate of dissociation of an insulin dimer into two monomers in water. The rate of this complex reaction is determined by multiple factors that are elucidated. By employing advanced sampling techniques, we first obtain the reaction free energy surface for the dimer dissociation as a function of two order parameters, namely, the distance between the center-of-mass of two monomers (R) and the number of cross-contacts (Q) among the backbone Cα atoms of two monomers. We then construct an orthogonal 2D reaction energy surface by introducing the reaction coordinate X to denote the minimum energy pathway and a conjugate coordinate Y that spans the orthogonal direction. The free energy landscape is rugged with multiple maxima and minima. We calculate the rate by employing not only the non-Markovian multidimensional rate theory but also several other theoretical approaches. The necessary reaction frequencies and the frictions are calculated from the time correlation function formalism. Our best estimate of the rate is 0.4 μs-1. Our study reveals interesting opposite influences of dimensionality and memory in determining the rate constant of the reaction. We gain interesting insights into the dimer dissociation process by looking directly at the trajectories obtained from molecular dynamics simulation.