Studies have shown that a combined application of several ion channel inhibitors immediately atfer cen-tral nervous system injury can inhibit secondary degeneration. However, for clinical use, it is necessary to determine how long atfer injury the combined treatment of several ion channel inhibitors can be delayed and effcacy maintained. In this study, we delivered Ca2+ entry-inhibiting P2X7 receptor antagonist oxi-dized-ATP and AMPA receptor antagonist YM872 to the optic nerve injury sitevia an iPRECIO@ pump immediately, 6 hours, 24 hours and 7 days atfer partial optic nerve transection surgery. In addition, all of the ion channel inhibitor treated rats were administered with calcium channel antagonist lomerizine hy-drochloride. It is important to note that as a result of implantation of the particular pumps required for programmable delivery of therapeutics directly to the injury site, seromas occurred in a signiifcant propor-tion of animals, indicating infection around the pumps in these animals. Improvements in visual function were observed only when treatment was delayed by 6 hours; phosphorylated Tau was reduced when treat-ment was delayed by 24 hours or 7 days. Improvements in structure of node/paranode of Ranvier and reductions in oxidative stress indicators were also only observed when treatment was delayed for 6 hours, 24 hours, or 7 days. Beneifts of ion channel inhibitors were only observed with time-delayed treatment, suggesting that delayed therapy of Ca2+ ion channel inhibitors produces better neuroprotective effects on secondary degeneration, at least in the presence of seromas.