A simple and highly sensitive chemiluminescence method to determine norfloxacin (NFLX) has been proposed by measuring the chemiluminescence (CL) intensities using a flow injection (FI) system. The CL intensity of the luminol-$H_2O_2$ system is strongly enhanced by the addition of Cu (II) in alkaline condition. The CL intensity is substantially increased after the injection of NFLX into the luminol-$H_2O_2$-Cu (II) system. The enhancement effect is attributed to a catalytic effect of Cu (II) due to the interaction with NFLX which forms a complex with the catalyst. Under the optimal conditions, the sensitizing effect of the CL intensity is proportional to the concentration of NFLX in the range of $1.5{ imes}10^{-9}-5.9{ imes}10^{-7}molL^{-1}$ (r = 0.9994) with a detection limit ($3{sigma}$) of $2.98{ imes}10^{-10}molL^{-1}$. The proposed method had good reproducibility with the relative standard deviation (RSD, n = 5) of 1.6% for $1{ imes}10^{-7}molL^{-1}$ of NFLX. The possible reaction mechanism of the CL reaction is also discussed. This method has been successfully applied for the determination of trace amount of NFLX in pharmaceutical preparations and serum samples.