Statement of the Problem: The purpose of placing sealants is to inhibit caries by physical closure of the pits and fissures of teeth. A device named DIAGNOdent is useful in detecting occlusal caries by employing laser fluorescence (LF). However, there are contradictory results in the influence of sealants on LF measurements.Purpose: The aim of this study is to investigate the effects of two different types of fissure sealants on LF measurements.Materials and Method: In this in vitro study, 86 extracted permanent third molars were divided randomly into two groups and clear or opaque sealant was applied on the occlusal surfaces. Two examiners performed pre- and post-seal fluorescence measurements twice with one week interval by employing DIAGNOdent device. Finally, measured values were evaluated through the statistical paired t-test by means of SPSS 17 software.Results: The mean value of LF measurements increased significantly due to the application of clear sealant (p= 0.001) while the statistical changes in this measurement was negligible after applying opaque sealant (p= 0.311).Conclusion: Clear sealants increase the LF measured values but opaque sealants cause almost no changes. Therefore DIAGNOdent device is not reliable for detecting caries beneath the clear sealant.Key Words: Caries; Laser Fluorescence; Pit and Fissure Sealants