We recently established an adrenal clock-disrupted transgenic mouse line (BMAS) that exhibits a dampened rhythm of corticosterone secretion and reduced amplitude of day/night activity. Here, we observe that voluntary wheel running increases the robustness and amplitude of both body temperature and home cage activity (HCA) rhythms in wild-type, but not in BMAS mice, but without affecting estrous cycle. Surprisingly, wheel running alters the HCA waveform of BMAS females in a way that preferentially increases the late nighttime (ZT21-ZT24) HCA. These results indicate that adrenal clock disruption causes the animals to respond differently to the voluntary exercise cue in middle-aged female mice.