BACKGROUND: It has been well documented that a long-time irradiation of the eye by a strong light elicits eyestrain and fatigue. To elucidate the mechanism for the induction of light-induced fatigue and asthenopia, changes in the mouse were analyzed after white light-irradiation to the eye. METHODS: C57BL/6j male mice were irradiated with white light in a specially designed room equipped with four mirrors covering all areas of its four walls to elicit diffused reflected light, and changes in their plasma levels of cortisol, INF-gamma, interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) were analyzed. RESULTS: Irradiation of mice with scattered white light significantly decreased the motional activity of animals, suggesting the occurrence of fatigue. Biochemical analysis and enzyme-immunoassay revealed that the irradiation of mice significantly elevated the plasma levels of cortisol, IFN-gamma, IL-10 and TGF-beta. All these changes were not observed with mice irradiated with the light in a similar room not equipped with mirrors. These changes were successfully inhibited by a polarized glass filter but not by a non-polarized filter with a similar absorbance. CONCLUSIONS: These observations suggest that irradiation of the eye by scattered reflected light stimulated a stress response via hypothalamo-pituitary-adrenal axis to enhance the secretion of cortisol from the adrenal grand and increase the plasma levels of cytokines.