Aim To investigate the effects of soluble epoxide hydrolase inhibitor (sEHi) on cardiac hypertrophy. Methods The pathology changes of the hearts were observed in the pressure overload mice and pressure overload mice fed with sEHi. Semi-quantitative RT-PCR was used to measure the expression of hypertrophy genes: atrial natriuretic peptide (ANP), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), skeletal muscle alpha-actin (SM ɑ-actin). Western blot was used to measure the changes of nuclear factor (NF)-κB complex. Results sEHi could significantly decrease both heart weight/body weight ratio and dimension of left ventricular end systolic chamber, increase fractional shortening. It could also reduce hypertrophy gene expression, and inhibit the activity of NF-κB. Conclusion sEHi might inhibit pressure overload induced cardiac hypertrophy through the effects on NF-κB pathway.