Seismicity rate changes in the Hellenic subduction zone (southern Aegean Sea) were studied by applying the Dieterich (1994) rate/state‐dependent friction model combined with static Coulomb stress changes (ΔCFF). The coseismic slip of the strongest earthquakes (with moment magnitude, Mw≥6.0) was considered to contribute to the stress field evolution along with the continuous tectonic loading. Stress changes were calculated just after each strong event, and their influence was examined in connection with the smaller magnitude earthquake occurrence rates. Qualitative and quantitative comparison between the observed seismicity rates (smoothed by the means of a probability density function) and the expected ones, as they were forecasted by the rate/state model, were investigated for the interseismic periods (study periods) between subsequent strong earthquakes. The calculations aim to identify areas of expected increased seismicity rates as candidates to accommodate enhanced seismic activity. Results strongly depend on the determination (smoothing) of the unperturbed (reference) seismicity rates and data adequacy. Seismicity rate results were filtered by certain criteria and constraints, in an attempt to overcome model uncertainties (epicentral errors, rupture models, parameter values) and to provide reliable results for specific areas of major interest, that is, in areas with increased positive Coulomb stress changes values. The modeling approach resulted in satisfactory correlation between observed and synthetic seismicity rates and, in particular, the two strong (Mw≥6) earthquakes that occurred in 2013 are located in areas of increased expected seismicity rates.