It is known that Kv1.3, KCa3.1, CRAC, TRPM7, and Clswell are five important ion channels in T lymphocytes. To investigate the mechanism underlying the protective effects of lentinan against T lymphocytes injury induced by chronic radiation in mice, we determined the expression profiles of Kv1.3, KCa3.1, Orai1, STIM1, TRPM7, and Clswell genes. Mice were injected with different concentrations of lentinan before exposure to 60Co g-ray. Total RNA was then extracted from T lymphocytes in murine spleen. The Real time-PCR was per- formed to detect the expression levels of Kv1.3, KCa3.1, Orai1, STIM1, TRPM7, and Clswell genes. The results show that, out of the six ion channels gene expression detected in the present study, only Kv1.3 and Orai1 were altered by lentinan in mice under chronic radiation stress. Kv1.3 and Orai1 expression were significantly elevated in T-lymphocytes isolated from irradiated mice, and were normalized by lentinan treatment. Our results suggest that that Kv1.3 and Orai1 channels may mediate the anti-radiation effects of lentinan.