Abstract: A column switching HPLC method was established for the determination ofnorfloxacin, and active dissociation product of silver norfloxacin ,in guinea pig plasma and tissues.The pre-treating column(50 mm×5mm ID)and analytical column( 150 mm×5mm ID )werepacked with μ-Bondapak C₁₈ ,37～50μm and YWG- C₁₈, 10μm,respectively. A mixture ofCH₃OH—0. 008 mol/L phosphate buffer—.05 mol/L tetrabutylammoniun bromide(25 :75 :4)was used as the analytical mobile phase with a flow rate of 1 ml/min. The pre-treating mobile phasewas 0.008 mol/L phosphate buffer with a flow rate of 3 ml/min. UV detection was made at 280 nm.The results were linear within a range of 2～128μg/ml norfloxacin for plasma,The lowest detectionlimit was 0.25μg/ml for plasma. The mean recovery of the method was 102%with a relativestandard deviation of less than 7%.