Xingnao enema (XN) has been commonly used to treat intracerebral hemorrhage (ICH) in China with good therapeutic effect. As very little is known about the mechanism of action of XN, the purpose of this project was to investigate the neuroprotective effect of XN on ICH model rats and to explore the underlying mechanisms of this therapy. In this study, experimental ICH was induced by the administration of stereotaxic collagenase type VII into the caudate nucleus. XN (at a high dose and a low dose of 3.60g·kg-1 and 1.80g·kg-1, respectively) was administered via enema. The detection of neuronal apoptosis was measured by TUNEL assay. Using immunofluorescence, the expression of claudin-5, ZO-1 and VE-cadherin was detected. The expression of DNA methyltransferase 3b (DNMT3b) and Matrix metalloproteinase-9 (MMP-9) was evaluated by western blot. And microRNA-29b was identified using quantitative real-time PCR. 3). Compared with the Model group, the group treated with XN had a significantly reduced number of dead neurons in hippocampus and cortical regions of ICH rats. Furthermore, this treatment significantly increased protein expression of claudin-5, ZO-1 and VE-cadherin while protein expression of DNMT3b and MMP-9 were significantly inhibited. Finally, microRNA-29b level were also lower than the Model group. Our data suggests that XN has significant neuroprotective effects on the ICH model rats, which might help to protect the blood brain barrier by regulating of a cascade including the expression of microRNA-29b which regulates DNMT3b that in turn regulates level of MMP-9.