Dental caries which is one of the most common chronic disease complexly developed by the action of oral bacteria, diet, and host factor. Various prevention program enhance resistance of demineralization and reduce the acidogenecity of oral bacteria have been introduced, representative material is fluoride and chlorhexidine. The purpose of the study was to evaluate and compare effectiveness of fluoride varnish and chlorhexidine varnish in vivo. Bovine tooth specimens were implanted in the lower space maintainers and applied with fluoride varnish and chlorhexidine varnish. After seven days in oral environment, metal mesh was covered to make similar condition of plaque accumulation and induce caries. All specimens were analysed by EPMA to evaluate quantitative change of Ca, P and by polarized microscope to identify histological changes. The results were as follows : After initial artificial caries induction in the mouth, there were remarkable enamel caries lesion in the control group under polarized light microscopy. The highest amount of mineral decrease were showed in control group. No statistically significant mineral decrease were showed in fluoride varnish group, while chlorhexidine varnish group showed only significant decrease of P(P<0.05). In conclusion both fluoride varnish and chlorhexidine varnish seemed to be effective for protecting enamel surface from caries activity, although fluoride varnish has more anticariogenic effect than chlorhexidine varnish.