In the modification of the fibrinogen fragment related sequences ARPAK, QRPAK GRPAK and KRPAK, the corresponding cyclo-ARPAK, cyclo-QRPAK, cyclo-GRPAK, and cyclo-KRPAK were prepared in the diluted solution. The bioassay in vivo indicated that the thrombolytic potencies of cyclo-ARPAK, cyclo-GRPAK, cyclo-QRPAK, and cyclo-KRPAK were significantly higher than that of ARPAK, QRPAK, GRPAK, and KRPAK. In water, the cyclopeptides were incubated with pepsin or trypsin at 37 C for 64h. There was no degradation product observed, on the other hand, with the same condition, the peptides were completely hydrolyzed in 8h. The relationships among the rigidity or the conformation and the thrombolytic activity in vivo and the stability to enzyme-induced hydrolysis in vitro of the cyclopeptides were discussed.