Background: Glucosyltransferase (GTF) of Streptococcus mutans catalyze sucrose to produce glucan ƒÑ(1„
³3), as a precursor of dental plaque. GTF activity can be inhibited by salivary sIgA in vitro. Objective: Oral mucous topical immunization (OMTI) using GTF isolate from S. mutans as an antigen might inhibit production of dental plaque, acid formation, and dental caries due to production of salivary anti-GTF sIgA. Methods: A pre and post-treatment block randomized control group design was conducted to investigate the effect of GTF oral mucous topical immunization on dental caries. GTF was purified from S. mutans INA99 serotype c, and was applied by OMTI on rat's that inoculated by S. mutans INA99 and the food was added with 20% of sucrose. Thirty rats were divided into 3 groups, group one was OMTI GTF, group two was OMTI using killed S. mutans, and group 3 as a control. The oral mucous topical immunization and S. mutans inoculation were given one time every two days until eleven days. Before immunization, caries score were detected using liquid caries detector and explorer, and 8 weeks after immunization were detected histological. Results: The result showed a significant difference (F = 5.43; p < 0.01) between GTF group (2.10 ± 1.45), S. mutans group (2.50 ± 1.78), and control group (4.90 ± 1.66). OMTI using GTF (0.20 ± 0.63) was less increase than OMTI using killed S. mutans (0.60 ±0.84) and control group (3.10 ± 1.91) as tested using multiple comparison. Conclusion: It is concluded that oral mucous topical immunization using GTF will prevent dental caries formation.