BACKGROUND Reversing hypertensive ventricular remodeling could reduce cardiovascular disease, but it’s reversal rate is low. Neutrophil Peptide 1 ( NP-1 ) is under intensive investigation as a potential therapeutic agent. But it’s role in hypertensive ventricular remodeling remains unclear. METHODS We collected data from hypertensive patients and measured NP-1 levels using an ELISA. We established hypertensive ventricular remodeling models and then treated with NP-1 or BAY 11-7082, an inhibitor of NF-кB. The cardiac hypertrophy markers and NF-кB factors were detected through HE, Masson, IHC, qPCR, and WB. We also established hypertrophic cardiomyocyte models and then dealt with NP-1 or BAY 11-7082. The myocardial hypertrophy indicators and NF-кB factors were measured by IF, qPCR, and WB. RESULTS We found the NP-1 level was decreased in patients with hypertensive ventricular remodeling. It’s demonstrated that NP-1 expression was decreased in hypertensive ventricular remodeling models. While NP-1 treatment has the potential to raise NP-1 levels and reverse ventricular remodeling. It’s also noticed a decrease with NP-1 in hypertrophic cardiomyocyte models. NP-1 disposal could improve NP-1 expression and reverse cardiomyocyte hypertrophy. Besides, our study found the activation of NF-кB in animal and cell models. And it could be inhibited by dealing with NP-1, which was similar to an inhibitor of NF-кB. CONCLUSIONS NP-1 could reverse ventricular remodeling and cardiomyocyte hypertrophy through inhibiting the activation of NF-кB. This may serve as a potential therapeutic target for cardiovascular disease.