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Purpose: The long-term effects of the development of chronic metabolic diseases such as type 2 diabetes and obesity have been associated with nutritional insults in critical life stages. In this study, we evaluated the effect of a low-protein diet on metabolism in mid-adulthood male rats. Methods: At 90 days of age, Wistar male rats were fed a low-protein diet (4.0 %, LP group) for 30 days, whereas control rats were fed a normal-protein diet (20.5 %, NP group) throughout their lifetimes. To allow for dietary rehabilitation, from 120 to 180 days of age, the LP rats were fed a normal-protein diet. Then, we measured body composition, fat stores, glucose-insulin homeostasis and pancreatic islet function. Results: At 120 days of age, just after low-protein diet treatment, the LP rats displayed a strong lean phenotype, hypoinsulinemia, as assessed under fasting and glucose tolerance test conditions, as well as weak pancreatic islet insulinotropic response to glucose and acetylcholine ( p < 0.01). At 180 days of age, after poor-protein diet rehabilitation, the LP rats displayed a slight lean phenotype ( p < 0.05), which was associated with a high body weight gain ( p < 0.001). Additionally, fat pad accumulation, glycemia and insulinemia, as well as the pancreatic islet insulinotropic response, were not significantly different between the LP and NP rats ( p > 0.05). Conclusions: Taken together, the present data suggest that the effects of dietary restriction as a stressor in adulthood are reversible with dietary rehabilitation, indicating that adulthood is not a sensitive or critical time window for metabolic programming. [ABSTRACT FROM AUTHOR]