In this work the deactivation of an ionic exchange resin, used as catalyst for promoting the esterification of fatty acids for producing biodiesel, has been studied. At this purpose, a dynamic mathematical model, suitable to describe the performances of a continuous tubular reactor containing the catalysts mixed with stainless steel springs as inert diluent, and its evolution with time due to the catalyst deactivation, has been developed. Experimental runs, performed in a pilot plant tubular reactor on fatty acid mixtures (oleins), are reported in the paper. The catalyst deactivation has been shown to depend mainly on the poisoning effect of iron that was present as impurity in the fatty acids used as feedstock. Some information about catalyst regeneration is also given at the end of the paper.