A simple, fast, economical, accurate, precise and reproducible RP – HPLC method was developed for the determination of Glimepiride (GLM) and Pioglitazone HCl (PIO) was developed on shimadzu HPLC systems with Inertsil ODS C18 column (150 × 4.6mm, 5μ) and using a mobile phase mixture containing mixed phosphate buffer and acetonitrile in the ratio of 40:60.The flow rate was 1.5 ml/min and the effluent was monitored at 225nm. The retention time of Glimepiride and Pioglitazone HCl were 3.06 and 1.97 min respectively .The method was validated in terms of linearity, precision accuracy, specificity and system suitability parameters. Linearity of Glimepiride and Pioglitazone HCl were in the range of 1.32 -7.92μg/ml and 10 - 60μg/ml .The percentage recoveries of both the drugs were 99.78% and 100.10% for GLM and PIO respectively from the tablet formulations .The proposed method’s results were found to be satisfactory and is suitable for simultaneous determination of Glimepiride and Pioglitazone HCl for routine quality control of drugs in bulk drug and formulation.