Previous researches carried out on the metabolism of sorbitol in the rat showed the influence of this polyalcohol on the activity of some dehydrogenases NAD and NADP-dependent and on lacate/pyruvate, NADH/NAD and NADPH/NADP ratios. Since sorbitol dehydrogenase (SDH, EC 1.1.1.14) is an enzyme with a great affinity for sorbitol, it seemed interesting to investigate the effect of a sorbitol-enriched diet on SDH activity in the rat liver after different periods of dietary treatment (20, 40, 60 days). SDH was assayed by a continuous optical test according to Bücher et al. The data obtained show a repressive action on SDH activity by a sorbitol-enriched diet. In fact, whilst after 20 days of treatment SDH activity decreased of about 18% in respect of the controls, after 60 days a decrease of 80% was observed. This result is so interesting to stimulate other investigations in vitro on the kinetics of such metabolic reaction in the attempt to explain the relation between the enzyme and its substrate.