Objective To investigate the role of p38 mitogen-activated protein kinase (p38 MAPK) in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH).Methods A total of 54 adult male Sprague-Dawley (SD) rats were equally and randomly divided into SAH group, control group, and p38 MAPK intervention group. An SAH model was established using intravascular silk puncture. The intervention group was given an intracerebroventricular injection of SB203580 (a specific inhibitor of p38 MAPK) at 30 minutes before modeling. All SD rats were sacrificed at 24 hours after modeling. The brain water content and neurological function score were determined. The expression of p38 MAPK in the brain was measured by RT-PCR and immunohistochemistry.Results The SAH group had significantly higher brain water content and mRNA level of p38 MAPK and a significantly lower neurological function score compared with the control group (t=-196.35, P<0.01; t=-24.75, P<0.01; t=201.08, P<0.01). The p38 MAPK intervention group had significantly lower brain water content and mRNA level of p38 MAPK and a significantly higher neurological function score compared with the SAH group (t=75.67, P<0.01; t=9.43, P<0.01; t=-81.68, P<0.01). The immunohistochemistry results showed that p38 MAPK protein was expressed only in the SAH group and the p38 MAPK intervention group, and the p38 MAPK group had significantly lower expression of p38 MAPK protein than the SAH group (t=-3.37, P<0.01).Conclusions p38 MAPK plays an important role in the formation of EBI, and it may be a new drug target for the prevention and treatment of EBI.