Abstract: In order to obtain the drugs with broader antibacterial spectrum, better antibacterial effect and less side-effect, modifications with lipid solublity group at the position of piperazinyl of ciprofloxacin were done. According to the prodrug design principle, a series of analogues were prepared and their biological activities were tested. The structures of the ten new compounds were confirmed by ¹H NMR, ¹³C NMR, ESI-MS and elemental analysis. The lipid solublility of the new compounds was better than that of ciprofloxacin. The results of antibacterial activity in vitro showed that most of the target compounds possessed relatively high inhibiting activity on Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity of the target compound 3d was higher than that of ciprofloxacin against Escherichia coli.