OBJECTIVES: To develop and validate simple, sensitive and selective HPLC method for determination of glipizide in human plasma.  METHODS: Liquid-liquid extraction method was used to extract glipizide from the human plasma samples. Chromatographic separation of glipizide was achieved using C18column (ZORBAX ODS 4.6 X 150mm). The mobile phase was comprised of 0.01 M potassium dihydrogen phosphate and acetronitrile (65:35, v/v) adjusted to pH 4.25 with glacial acetic acid. The analysis was run at a flow rate of 1.5 ml/min with an injection volume was 20 µL. The UV detector was operated at 275 nm. The proposed method was validated as with respect to selectivity, linearity, accuracy, precision, recovery, limit of quantification (LOQ) and stability.  RESULTS: The calibration curve was linear over a concentration range of 50 – 1600 ng/mL. Intra-day and inter-day precision and accuracy values were below 15%. The limit of quantification was 50 ng/mL and the mean recovery was above 98%. Freeze-thaw, short-term, long-term and post-preparative stability studies showed that glipizide in plasma sample was stable.  CONCLUSIONS: A rapid, simple, selective and sensitive HPLC method for determination of glipizide in human plasma was successfully developed. The method showed good recovery, accuracy and precision. The method can be successfully applied to in pharmacokinetics and bioequivalence studies to quantify glipizide in plasma samples.