Restraint stress has been reported to suppress the conventional T and B lymphocyte responses, while inversely activating the granulocyte response in the peripheral blood. Since royal jelly (RJ) helps the body to cope with stress and fatigue, we asked whether RJ could restore the stress-induced dysregulatory numbers of lymphocytes and granulocytes in the peripheral blood and different organs such as the spleen, liver and thymus. In unstressed mice, we did not observe any significant change in the number of these immune cells in the peripheral blood and organs examined, regardless of the administration of RJ and PBS as a control. On the other hand, the mice which were subjected to the restraint stress without RJ administration showed significantly decreased numbers of total lymphocytes, including both T and B lymphocytes, but a significantly higher granulocyte number in the peripheral blood. The stress also affected a decrease in the total MNCs in the spleen and thymus. The RJ administration to these stressed mice showed a significant effect to restore the dysregulatory number of total lymphocytes, T and B lymphocytes, and granulocytes in the peripheral blood. The RJ administration to the stressed mice also partially restored the absolute numbers of total MNCs in the thymus, which was prone to the development of severe atrophy. These findings provide interesting evidence that RJ did not affect the immune function in the normal situation but exhibits an anti-stress effect through the well-balanced restoration of the dysregulation of immune cells under the stressed condition.