To analyze the different responses of NK cell subsets isolated from the patients with proceeding multiple sclerosis to interferon-beta.NK cells were isolated from the patients' peripheral blood mononuclear cells, separated into two subsets: CD94/NKG2A-bright and CD94/NKG2A-dim and then sorted by flow cytometry. The two subsets were cultured with IFN-beta to evaluate CD94/NKG2A expression pattern and the corresponding cell proliferation and secreted IL-10 and TGF-beta.The positive NK cells of CD94/NKG2A made up 25.5% within the whole NK population. Among them, CD94/NKG2A-bright and CD94/NKG2A-dim amounted to 23.6% and 76.4%, respectively. When INF-beta was added to two groups, the proliferation rate of CD94/NKG2A-bright group was much lower than that of CD94/NKG2A-dim group and its expression pattern didn't alter greatly. In contrast, the expression of CD94/NKG2A in CD94/NKG2A-dim group was markedly increased. IL-10 and TGF-beta secretion was increased dominantly compared with the two untreated groups. There were great differences between the secreted IL-10 and TGF-beta in the stimulated groups.IFN-beta can inhibit NK cells by inducing the inhibitory expression of CD94/NKG2A and stimulate IL-10 and TGF-beta secretion. CD94/NKG2A-bright group and CD94/NKG2A-dim group make different reaction to IFN-beta.