The purpose of this work is to model the multi-scale behavior of active clays using the Discrete Element Method (DEM). In particular, great importance is given to the relationship between the behavior of the clay at the micro-scale and the macroscopic behaviour under the effects of mechanical and chemical loads. The calibration of the parameters describing the behaviour of the aggregations of clay particles was done by using the results of microstructural observations, which were tuned to reproduce the compression of samples of the same material loaded at different pore fluid concentrations, maintained constant during loading. A good reproduction of the experimental results was obtained.