Background: Pit and fissure sealing is an effective method to prevent cavities in young permanent teeth. A study was conducted to evaluate the effect of high-irradiance light-curing with a shorter time on the microleakage of resin fissure sealant (ClinproTM , 3M ESPE, USA). Methods: 100 extracted human molars and randomly divided them into five groups (n = 20) based on the light-curing unit used. Group A1 used acid etching for 30 seconds and then 1000 mW/cm2 light-curing for 20 seconds. Group A2 used acid etching for 30 seconds and then 3200 mW/cm2 light-curing for 6 seconds. Group B1 used adhesive 1000 mW/cm2 light-curing for 20 seconds and then fissure sealant 1000 mW/cm2 light-curing for 20 seconds. Group B2 used adhesive 1000 mW/cm2 light-curing for 20 seconds and then fissure sealant 3200 mW/cm2 light-curing for 6 seconds. Group B3 used adhesive 3200 mW/cm2 light-curing for 3 seconds and fissure sealant 1000 mW/cm2 light-curing for 20 seconds. After 250 thermocycles, the specimens were sectioned and examined under a stereomicroscope and scored for marginal microleakage. Results: All groups showed microleakage. However, after pre-treatment with a self-etching adhesive at 3200 mW/cm2 light-curing for 3 seconds (B3 group), there was a significant increase in microleakage, which was significantly higher than the other groups (p < 0.05). There was no significant difference in microleakage in the remaining groups (p > 0.05). Conclusions: High-irradiance shorter time light-curing patterns did not significantly affect the microleakage of Clinpro fissure sealant. However, further clinical studies, including randomized clinical trials, are needed to evaluate its clinical use. The self-etching adhesive did not increase the microleakage of the pit and fissure sealant under normal light intensity and exposure time. But, if a high-intensity short-time irradiation mode was used in adhesive curing, it resulted in severe microleakage, so it should be avoided in clinical practice.