Abstract: AIM: Using two kinds of osteoblast-like cell lines TE85 and U2 as cell models, the molecular mechanism of 17β-estradiol (E₂) in regulating cell function was studied. METHODS: Using methods of ³H-thymidine incorporation for cell proliferation, ELISA for IL-6 content measurement and transferring L-³H-arginine to L-³H-citruline for iNOS activity. RESULTS: In two cell lines，interleukin-1(IL-1, 20 U*mL-1) and tumor necrosis factor (TNFα 50 U.mL^-1) stimulated osteoblast to secret IL-6 after treatment for 48 h. At the same concentration, IL-1 and TNFα reduced the intracellular protein content resulting from cell proliferation inhibition. In TE85 cells, E₂ reduced the IL-6 secretion and inhibited the influence of IL-1 and TNFα on the cell proliferation. After L-NMMA, an inhibitor of NOS, was added, the ³H-TdR uptake decreased in a dose-dependent fashion in TE85 and U2 cells. When the cells were treated with E₂ and L-NMMA concomitantly, the inhibiting effects of the latter were diminished and the percentage of ³H-TdR uptake reached normal levels. Besides that, IL-1 and TNFα increased intracellular iNOS activity significantly, which was higher than that of E₂. CONCLUSION: E₂ regulated cell function by way of reducing IL-6 secretion and improving iNOS activity.