An oral route of drug administration is most preferred rout of delivery, as it is convenient and ease of ingestion. One of the disadvantages of this rout is low bioavailability, as most of the drugs have poor solubility in water. In the case of poorly water-soluble drugs (BCS Class II and IV), dissolution is the rate-limiting step in the process of drug absorption. Cyclodextrins are widely used for to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of poorly soluble drug molecules. Glimepiride, is an antidiabetic drug, has poor solubility in water (BCS class II).The phase solubility studies were carried out to study the effect of cyclodextrins according to the method described by Higuchi and Connors. The phase solubility studies indicated formation of Glimepiride-β-CD inclusion complexes at 1:1 M ratio in phosphate buffer pH 6.8, pH 7.2 and pH 7.4,with stability constant of 319.79 M-1, 518.23 M-1and 272.82 M-1respectively. Similarly, the phase solubility studies indicated the formation of Glimepiride-HP-β-CD inclusion complexes at 1:1 M ratio in phosphate buffer pH 6.8, pH 7.2 and pH 7.4 with stability constant of 342.41 M-1, 985.42 M-1 and 226.21 M-1respectively. The statistical analysis indicated that, solubility of Glimepiride was markedly enhanced by complexation with β-CD and HP-β-CD in different pH. An inclusion complex of glimepiride with HP- β-CD was found to be more stable than β-CD at pH 7.4.