Aim To investigate whether tetramethylpyrazine can suppress oxidative stress and improve sympathetic neural remodeling in rats following myocardial infarction (MI). Methods A total of 40 male Sprague-Dawley rats were involved in this study. The animals were randomly divided into three groups:control group (n=10), MI group (n=15) and treated group (n=15). MI model was established by ligating left anterior descending artery of rats. Rats in treated group were intraperitoneally injected with tetramethylpyrazine at 120 mg/kg per day for 6 weeks post MI. The control group experienced the same procedure but ligation. Six weeks after operation, echocardiography and serological examination were performed to determine cardiac function, superoxide dismutase (SOD) and malondialdehyde (MDA) in each group. Myocardial nerve density was determined in infarct marginal zone by immunohistochemistry staining with anti-tyrosine hydroxylase (TH) antibodies. Liner regression analyses were also performed to examine whether level of oxidative stress were associated with sympathetic neural remodeling. Results The left ventricular end diastolic diameter in diastole (LVEDD) and left ventricular end systolic diameter (LVESD) of MI group were higher than those of control group, while ejection fraction (EF)and fractional shortening (FS) were lower than those of control group (all P<0.05).LVEDD and LVESD were significantly reduced in treated group, as compared with the MI group, while EF and FS were significantly increased in treated group, as compared with the MI group (all P<0.05). SOD content was significantly increased and MDA significantly reduced in treated group, as compared with MI group (P<0.05 and P<0.01, respectively). TH-positive nerves were more abundant in the infarct marginal zone in MI group compared to control group, while TH-positive nerve density were reduced in treated group compared to MI group (all P<0.01). Linear correlation between value of MDA/SOD and density of TH-positive nerve has been determined (r=0.909, P<0.01). Conclusion Tetramethylpyrazine can suppress sympathetic neural remodeling process after MI via attenuated oxidative stress, which may in turn leads to a promising treatment for the malignant ventricular arrhythmias post MI.