Objective To investigate the transformation of microhardness and microstructures of human dental fluorosis after demineralization and remineralization in vitro. Methods Forty human dental fluorosis enamel blocks were demineralized by acid-etching gel, then subjected to 1.0% casein phosphopeptides stabilized calcium phosphate(CPPCP) for remineralization. Surface enamel microhardness was measured on the enamel blocks before and after demineralization and after remineralization. The enamel specimens was observed by stereomicroscope and scanning lectron microscope, then sectioned(100 μm) and examined by transmission light microscope and polarized light microscope. Results Before demineralization, the average knoop hardness value of the fluorosed teeth was(241.53± 21.31)kHV. After demineralization, obvious decrease of the surface hardness of the enamel was observed, the mean value was(175.76±24.99)kHV(P<0.05), the percent of the surface microhardness demineralization(%SMHD) was(27.23± 4.79)%, and major demineralization was under the surface of the enamel, which was similar to the early natural enamel caries. After remineralization, obvious increase of the surface hardness of the enamel was observed, the mean value was(210.17 ±21.48)kHV(P <0.05), the percent of the surface microhardness remineralization(%SMHR) was (52.32±4.23)%, major remineralization was under the surface of the enamel. Conclusion Remineralization could be used to prevent and cure the early natural enamel caries of fluorosed dental teeth.