Purpose. The purpose of this study was to monitor stem cell differentiation by glycogen synthesis kinase-3 (GSK-3) inhibitors in induced palatal ulcer in rabbits and its possible effect of regeneration. Materials and Methods: One hundred and sixty-two adult male rabbits were used. Rabbits were divided into 3 groups, then each group divided into 3 subgroups (18 for each subgroup) according to the date of scarification at 1, 7, 14 days postoperatively. Group (I): Control group, the rabbits didn't subject to any surgical procedure. Experimental groups; Group (II): (-ve control), the palatal mucosal ulcer was induced and allowed to heal normally. Group (III): (+ve control), the palatal mucosal ulcer was induced and Tideglusib solution was applied daily. Results: at 1 and 7 days, the minimum imply has been recorded in group (I), after that group (II), although the highest amount has been documented in group (III). while at 14 days, the minimum amount has been documented in group (I), tracked closely by group (III), while the highest amount has been recorded in group (II). Conclusion: We provide that topical application of Tideglusib on the palatal mucosal ulcer reduced inflammation, increased collagen deposition, enhanced stratifications of the oral epithelium and accelerated wound closure. Therefore, Tideglusib therapy could be a promising therapeutic modality for oral ulcers and wounds.