Hydrogen sulfide (H2S) is a gasotransmitter which regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, H2S donor) is able to prevent left ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30 and 90 µmol·kg-1·d-1), combination of NaHS (30 µmol·kg-1·d-1) and glibenclamide (5 mg·kg-1·day-1), glibenclamide (5 mg·kg-1·day-1), hydralazine (10 mg·kg-1·day-1) and placebo for 3 months. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 µm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes as well as DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated dienes levels. The cardioprotective effects were blunted by co-administration of glibenclamide, suggesting a role of ATP sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure as compared with NaHS treatment, however, it exerted no effect on the remodeling process nor on ROS and conjugated dienes levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels whereas, DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment is worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.