A rapid and novel method combining dispersive liquid-liquid microextraction and high-performance liquid chromatography coupled with fluorescence detection was developed for the determination of donepezil in human urine. Parameters affecting extraction efficiency and chromatographic determination, such as the type and volume of the extraction and disperser solvent, pH of sample for dispersive liquid-liquid microextraction, mobile-phase composition, pH, column oven temperature, and flow rate for chromatographic determination, were evaluated and optimized. Using a C-18 core-shell column (7.5 x 4.6 mm, 2.7 mu m), the determination of donepezil was accomplished within 5 min. Under optimum conditions, developed method was linear in the range of 0.5-25 ng mL(-1) with the correlation coefficient >0.99. Limit of detection was 0.15 ng mL(-1). The relative standard deviation at three concentration levels (2, 12.5, and 20 ng mL(-1)) was less than 11% with accuracy in the range of 96.9-102.8%. The results of this study demonstrate that the use of dispersive liquid-liquid microextraction and core-shell column can be considered as a powerful tool for the analysis of donepezil in human urine.