A simple reverse phase liquid Chromatographic method has been developed and subsequently validated for simultaneous determination of Pioglitazone and Glimepiride in combination. The separation was carried out using a mobile phase of phosphate buffer (pH-4.5): Acetonitrile (45:55) v/v and using methanol as diluent. The column used was Inertsil ODS (250 mm x 4.6 mm i.d., 5?m) with flow rate of 1 ml/min using UV detection at 225 nm. The described method was linear over a concentration range of 5-50?g/ml and 5-25 ?g/ml for the assay of Pioglitazone and Glimepiride respectively. The retention times of Pioglitazone and Glimepiride were found to be4.6 and 7.7min respectively. Results of analysis were validated statistically and by recovery studies. The results of the study showed that the proposed RP-HPLC method is simple, rapid, precise and accurate, which is useful for the routine determination of Pioglitazone and Glimepiride bulk drug and in its pharmaceutical dosage form.