Purpose: The study was conducted to investigate effects of cyclodextrins (CyDs) on crystallizations and polymorphic transitions of oral hypoglycemic agents, tolbutamide and chlorpropamide, in aqueous solution.Methods: The drugs were dissolved in alkaline solutions,followed by titration with HC1 and the solutions were stored at 4 ℃ for crystallization.The contents of polymorphs in the precipitates were determined by powder X-ray diffractometry.Results: Tolbutamide crystallized to the metastable Form Ⅳ polymorph in the presence of 2,6-di-O-methyl-β-cyclodextrin (DM-β-CyD), whereas in the absence of DM-β-CyD it crystallized to the stable Form Ⅰ.Similarly, chlorpropamide crystallized to the metastable Form Ⅲ polymorph in the presence of DM-β-CyD, whereas to the stable Form A in the absence of DM-β-CyD.Conclusion: The results indicated that DM-β-CyD significantly inhibits the solution-mediated polymorphic transition of the metastable forms of the drugs that occur at an early stage of crystallization according to the Ostwalds Rule of Stages.The complexation with DM-β-CyD may be useful for the preparation of metastable forms of drugs.