Objective To compare the neuroprotection effect of two methods of Lidocaine administration in rabbit model of subarachnoid hemorrhage. Methods Forty New Zealand white rabbits were randomly divided into sham group, subarachnoid hemorrhage group (SAH), Lidocaine intravenous injection group (L1), and Lidocaine intracisternal administration group (L2). The rabbits were given general anaesthesia, then 1.5 mL autologous nonheparinized arterial blood was injected into cisterna magna to establish SAH model, while 1.5 mL saline was used in sham group. Thirty minutes later, the rabbits in L1 and L2 group respectively received 0.3 mL 2% Lidocaine administration of intravenously and intracisternally injection. All animals were sacrificed at 72 h after SAH. The samples of basilar artery and hippocampus tissue were processed for morphometric analysis. At pre-operation and 72 h after SAH, the level of interleukin-6 (IL-6) in serum was measured. HE staining and C fos immunohistochemical staining were performed in L1 and L2 groups. Artery area and artery diameter of basal arteries, normal neuron density and C-fos positive cell in hippocampus were measured at 72 h after SAH. Results The baseline level of IL-6 was not significant different in four groups (P>0.05). The level of IL-6 at 72 h after SAH was significantly higher than that at pre-operation in SAH, L1 and L2 groups (PPP