A lot of clinical studies have reported that dry eye disease is closely associated with psychiatric disorders such as depression and anxiety. Using a forced swim test, we investigated the effect of chronic ocular dryness on a depression-like behavior. The exorbital lacrimal glands (ELG) or exorbital and intraorbital lacrimal glands (ELG+ILG) were bilaterally excised from 8-9 weeks old male C57BL/6J mice resulting in persist reduction of tear volume. The ELG+ILG excision exhibited more severe corneal damage than the ELG excision. In the forced swim test, ELG excision mice showed significant longer immobility time than sham operation mice at 12 weeks post-surgery, although there was no significant difference between the groups at 6 weeks. The ELG+ILG excision mice showed higher immobility even at 6 weeks. After treatment of wheel-running apparatus for 3 days, the longer immobility times in the forced swim disappeared in both models. Our results suggest that dry eyes might directly cause a depressive disorder that depends on the severity and duration of the symptoms, and that voluntary motor activity could help recovery from a depressive state induced by dry eyes.