The activation/deactivation processes of chromia occurring during the heterogeneous catalyzed isomerization reaction of 1,1,2,2-tetrafluoroethane were investigated. It was proved that coke formation on acid sites of the solid is mainly responsible for the observed slow decrease in the catalytic activity. Oxygen treatment removes the coke deposits almost completely. Enhanced catalytic activity results from the oxygen posttreatment. By means of CO as well as NH3IR and UV-vis spectroscopic measurements, it was shown that a relative increase in the strength of the acid sites took place. Since the active catalyst does not reveal any detectable Bronsted acidity before or after the oxygen treatment, one can conclude that Lewis acid sites alone are responsible for the catalytic cycles of the 1,1,2,2-tetrafluoroethane isomerization reaction. In addition, chromium was formed in higher oxidation states (Cr4+ and Cr5+) and was responsible for oxidative reactions during the gas phase as well as for the formation of CO2 and pentafluoroethane.