Purpose: In this study, the efficacy of a gel formulation containing Hp-HCl (a photosensitizer) dissolved in glycerin was evaluated for photodynamic treatment (PDT) of tumors. Methods: The release kinetics of water-dissolved Hp-HCl and glycerin-dissolved Hp-HCl from gel formulae were studied in vitro, where the latter showed faster drug release. The growth rates of tumor size in animals, from different treatment groups, were measured. Results: The group treated with the glycerin-dissolved Hp-HCl showed more significant decrease in tumor rate (smaller size) in comparison to the water-dissolved formula, after 35 post-implantation days. Histopathological examination of tumor sections revealed that glycerin-dissolved Hp-HCl effectively distributed the drug throughout the tumor, resulting in almost complete disappearance of tumor cells. Overall, the dissolution of Hp-HCl in glycerin not only increased drug release from the gel formulation but also improved its distribution and therapeutic efficiency. These findings were supported by histopathological results Conclusion: Suggesting that the topical use of Hp-HCl dissolved in glycerin holds promise for improved PDT.