Most living beings including human beings have endogenous 24-hr rhythms, called circadian rhythms. The most important factor to alter the circadian rhythms is light. Therefore, this biological rhythms can easily disrupt by exposure to light at night (LAN). In modern society, rotating shift work with night work (night shift work) is essential working arrangement and induces circadian disruption to workers by LAN exposure. Epidemiologic studies indicate that a long-term biological rhythm disruption induced by a long-term LAN exposure causes many serious health disorders including immune dysfunction. Cd also dysregulates the immune system. Main exposure source of Cd is tobacco smoking and food intake in living environment. Further, in work places with handling Cd, occupational environment also be an exposure source with high concentration of Cd. In this report, we paid attention to and examined the combined effect of Cd and LAN on immune system. Mice were kept under the light/dark shift condition and/or injected CdCl2 (0.33 or 1.0 mg/kg) twice a week for 4 weeks followed by sacrificing 7 days after the last injection. The mitogen activity induced by phytohemagglutinin was markedly reduced by shift condition; further, this reduced mitogen activity was completely inhibited by additional Cd treatment. This result indicates a possibility of enhancement of immune dysfunction by Cd and LAN combination. Our result suggests that Cd exposure when being the circadian disruption had potential for more inhibition of immune function.