Purpose: To investigate the effect of Glycogen Synthase Kinase-3 (GSK3) antagonist on pulp tissue repair in rabbits. Materials and Methods: 24 adult healthy male rabbits were used in this study divided into three main groups: Group I (control): 2 rabbits with normal teeth without pulp exposure. Group II (TG): The exposed pulps of right posterior teeth of 22 rabbits were capped with KolSpon in association with 34 nM Tideglusib. Group III (MTA): The exposed pulps of left posterior teeth of 22 rabbits were capped with Mineral Trioxide Aggregate (MTA). The 2 rabbits with normal teeth and 6 rabbits with pulp capped posterior teeth were euthanized after one day. Their DNAs were extracted and tested for expression of Axin2 and β-actin by qPCR. 8 rabbits were euthanized after 4 weeks, and another 8 was euthanized after 6 weeks. The teeth were collected and prepared for immunohistochemical study using anti- β-catenin antibody. Results: The qPCR results showed the higher expression of Axin2 in the Tideglusib group than control group (without treatment) by about 5 folds and about 1.5 fold in the MTA group. The immunohistochemical results revealed the increase intensity in the Tideglusib group than MTA at four weeks with no significance difference (p>0.05).Whilst after 6 weeks the higher expression was in Tideglusib group with significance difference (p < 0.05). Conclusion: The Tideglusib drug stimulates the expression of Axin2 transcription factor gene which is known to play a key role in regulation of odontoblast and osteoblast differentiation.