Objective To study the effects of NRG2 on cardiac structure and function, we established the cardiac-specific human NRG2 transgenic mice and investigate the effect of NRG2 on cardiac structure and function under pressure overload situation. Methods The transgenic vector was constructed by insertion of the human NRG2 gene under the α-MHC promoter. The transgenic mice were generated by microinjection and were all maintained on a C57BL/6J genetic background. The genotype of transgenic mice was identified by PCR and the expression level of target gene was determined by western blot. Transverse aortic constriction (TAC) was applied to prepare the pressure overload induced cardiomyopathy mice model. The cardiac structure and function of the transgenic mice were compared and analysized by echocardiographic and pathological observation. Results Transgenic mice with high level of NRG2 in heart tissues were established. The left ventricular wall thickness (LVPWD) was increased, and to 15.6% at 3 months old compared with that of the non transgenic (NTG) mice. The hypertrophy of left ventricular wall caused by pressure overload was removed due to the expression of NRG2. Meanwhile, cardiac disarray and fibrosis were increased obviously compared with that of the NTG mice. Conclusion The transgenic expression of NRG2 in heart tissues could shorten the pathological process of hypertrophy, but accelerated the process of heart failure (HF).