Rationale: Individuals who experience sleep loss may exhibit certain physiological abnormalities. Central stimulant drugs have been studied in sleep-loss conditions, and some of them might be therapeutically beneficial. Modafinil (diphenyl-methyl-sulfinyl-2-acetamide, MOD) has been increasingly employed for elevating alertness and vigilance in recent years, yet the underlying mechanism of actions for MOD is not fully understood. Objectives: To examine the behavioral effect of MOD following rapid eye movement sleep deprivation (REMD) in rats. A five-choice serial reaction time task (5-CSRTT) was employed to investigate animals' attentional performance and impulsive reactivity. Materials and methods: Rats of different ages were trained to learn the 5-CSRTT. REMD with the water platform method was applied for 96 h. The impacts of REMD on 5-CSRTT in middle-age (32-weeks-old) and young-adult (12-week-old) rats were compared with baseline or a condition with shorter visual stimulus duration. Results: The results revealed that following REMD, young-adult but not middle-age rats were liable to be affected in their performances of the 5-CSRTT. In young-adult rats, while MOD had no contributions to the effect of REMD, it worsened rats' performance following REMD when the stimulus duration was shortened, as shown by the reduced number of correct responses and prolonged magazine latency. Conclusions: These results suggest that aging might be a crucial factor for the physiological impact following REMD. MOD should be used cautiously, particularly, in conditions that require REM sleep.