Cerebral endothelial cell dysfunction plays a critical role in the pathophysiology of vascular injury subsequent to subarachnoid hemorrhage (SAH), yet the precise molecular mechanism remains largely speculative. Inflammation stands out as a pivotal contributor to an unfavourable prognosis post-SAH, with nuclear factor-κB (NF-κB) pathways being initiated and ultimately leading to inflammation activation and pro-inflammatory cytokine release following SAH. In this study, we explored the impact of the Coactivator-associated arginine methyl transferase 1 (CARM1) inhibitor TP-064 on inflammation in an in vitro SAH model. Exposure of endothelial cells to TP-064 resulted in a significant reduction in CAMR1 and NF-κB expression upon hemoglobin exposure. Similarly, endothelial cells treated with TP-064 following hemoglobin incubation exhibited decreased expression levels of intercellular adhesion molecule-1 (ICAM1), myeloperoxidase (MPO), and cytokine production including interleukin-1β (IL-1β), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) in response to hemoglobin exposure. Moreover, subsequent investigations demonstrated that CARM1 transcriptionally regulates NF-κB via methylation. Additionally, TP-064 notably mitigated endothelial dysfunction. Collectively, our findings identify TP-064 as a CARM1 inhibitor targeting inflammation and neutrophil infiltration, offering new insights into therapeutic strategies for addressing endothelial cell dysfunction following SAH.