Objective To explore the influence and possibly mechanism of intraperitoneal injection of protoporphyrin zine-IX (ZPP-IX) on the neurological function in rats with intracerebral hemorrhage (ICH). Methods Ninety-five rats were randomly divided into 4 groups: the normal group (re = 5) , ZPP-IX group (re =30) , ICH group (re = 30) , and DM-SO group (re = 30). In the ZPP-IX group, ICH group, and DMSO group, the rats were slowly injected w ith 50 p,L of autologous femoral artery blood to the basal ganglia on the brain stereotaxic apparatus to prepare the ICH model; the rats in the normal group were punched at the same position, without blood injection. In the ZPP-IX group, 10 mg/kg ZPP-IX was in-traperitoneally injected within 30 min after modeling. The rats in the DMSO group were given 10 mg/kg of 35% DMSO. The rats in the normal group and ICH group were given the same amount of normal saline. Garcia 18-test was used to evaluate the neurological function of rats. Western blotting was used to detect the protein expression of Nrf2 . binding-Nr£2 , HO-1 , NF-κB. and TNF-α. RT-PCR was used to detect the mRNA expression of Nrf2. binding-Nrf2. HO-1 , NF-κB. and TNF-ct. Double immunofluoresence staining method was employed to observe the co-expression of HO-1, Nrf2, NF-κB, TNF-ct and CD1 lb in the brain tissues. Results Compared with the normal group, the neurological function scores significant decreased in the ICH group, ZPP-IX group, and ZPP group at 6, 12, 24. 48. 72 h and 7 d (all P<0.05). Compared with the ICH group, the neurological function scores of the ZPP-IX group decreased at 12, 24, 48 , 72 h, and 7 d (all P<0. 05). The HO-1, Nrf2, NF-κB, and TNF-α levels significantly increased at 6, 12, 24, 48, 72 h and 7 d, while the binding-Nrf2 level significantly decreased in the ICH group as compared with those of the normal group (all P < 0. 05). Compared with the ICH group, the expression of HO-1 protein decreased in the ZPP-IX group at 12, 24.48,72 h and 7 d, and the expression of binding-Nrf2, NF-κB and TNF-α increased (all P <0.05). Compared with the normal group, the expression of HO-1 and Nrf2 mRNA in the ICH group and DMSO group increased at each time point after modeling, and NF-κB and TNF-α mRNA expression significantly increased at 24,48.72 h and 7 d (all P <0.05). Compared with the ICH group, the expression of HO-1 and Nrf2 mRNA decreased in the ZPP-IX group at 24,48, 72 h and 7 d, and the expression of NF-κB and TNF-α mRNA increased at each time point after modeling (all P <0. 05). Compared with ZPP-IX group, the positive cells with HO-1 and CD1 lb co-expression increased in the ICH group at 6, 12, 24.48, 72 h and 7 d, and the positive cells with co-expression of Nrf2 and CD1 lb increased in the ICH group at 12 , 24, 48, 72 h and 7 d (all P<0.05). Conclusion ZPP-IX aggravates the neurological impairment of ICH rats by inhibiting the HO-1 expression, then inhibiting the Nrf2 dissociating and entering nucleus, and activating the NF-κB and TNF-α expression. [ABSTRACT FROM AUTHOR]