A simple, rapid and sensitive high-performance liquid chromatographic (HPLC) method has been developed to quantify zolmitriptan in plasma using an isocratic system with fluorescence detection. The method included a single-step liquid-liquid extraction with methyl tertiary butyl ether. HPLC separation was carried out by reversed phase chromatography with a mobile phase composed of 0.05% (v/v) triethylamine in water(adjusting to pH 2.75 with 85% phosphoric acid) and acetonitrile (92:8, v/v), pumped at flow rate of 1.5 ml/min. Fluorescence detection was performed at 225 nm (excitation) and 360 nm (emission). The calibration curve for zolmitriptan was linear from 0.2 to 40 ng/ml. The validation method yielded good results regarding linearity, precision, accuracy, specificity and recoveries. The values of the limit of detection (LOD) and limit of quantification (LOQ) were 20 and 40 pg, respectively. The method was sensitive, simple and repeatable enough to be used in pharmacokinetic studies.