Indapamide belongs to the class of thiazide-type diuretic drugs and is widely used in the treatment of hypertension and nephrolithiasis. In this work, a simple, rapid and efficient low density solvent (LDS) based ultrasound assisted emulsification microextraction (USAEME) method combined with high performance liquid chromatography-variable wavelength detection (HPLC-VWD) was investigated for the determination of a popular drug of abuse, indapamide, in human urine samples. The target compound was extracted from acidified sample solution with a few microliter amount of LDS by a USAEME method. The influence of several important experimental variables such as selection of the extraction solvent and its volume, ultrasonication time, pH and ionic strength were thoroughly examined and optimized. Under optimal conditions, the calibration was linear in concentration range from 1–100 ng mL⁻¹ with a correlation coefficient of 0.9977 for the target analyte. The limit of detection based on signal to noise ratio of 3 was 0.3 ng mL⁻¹ and the relative standard deviations varied from 1.2–6.6%. The proposed method provides a rapid, sensitive, low cost, easy to handle, and convenient procedure to determine indapamide in human urine samples.