Objectives: Glucan ƒÑ(1„_3) as a precursor of dental plaque is catalyzed by Streptococcus mutans's glucosyltransferase (GTF) from sucrose. Oral mucous topical immunization (OMTI) using GTF isolate from S. mutans as an antigen might inhibit acid formation and decrease of caries activity. Methods: A pre and post-treatment block randomized control group design was conducted to investigate the effect of GTF oral mucosa topical immunization on caries activity. GTF was isolated from S. mutans INA99 (serotype c) using affinity chromatography. Thirty rats were inoculated by S. mutans INA99, the food was added with 20% of sucrose, and divided randomly into 3 groups. Group one was applied by oral mucosa topical immunization (OMTI) using pure 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 fourteen days. Before and 8 weeks after immu-nization, caries activities were measured using Cariostat. Results: The result of Kruskal-Wallis test showed a signifi-cant differences (H=19.9118; p<0.01) between OMTI using GTF, OMTI using killed S.mutans, and control. OMTI using GTF was more decrease in caries activity than OMTI using killed S. mutans as tested by Kruskal-Wallis multiple comparison, and there was no decrease of caries activity in the control group. Conclusions: It is concluded that topical immunization using GTF isolate from Streptococcus mutans at oral mucosa will decrease the caries activity.