Objective: To evaluate whether treatment with sodium hydrogen sulfide (NaHS) improves cardiac function and remodeling of two kidney-one clip (2K-1C) rats through inhibition of matrix metalloproteinase (MMP) activity and oxidative stress. Design and method: 2K-1C hypertension was surgically induced in male Wistar rats (200 g; ethics commitee #118/2019) by an implantation of a silver clip (0.2 mm) in the left renal artery. Control rats (2K) was submitted to laparotomy. SBP and echocardiograph were registered. The NaHS (0.24 mg/Kg/day; i.p.) treatment or vehicle (0.6% DMSO in saline; i.p.) was initiated in the second week after the surgeries and lasted for 28 days. Hearts were collected and western blotting to MMP-2, Nox2 and Nox4 were performed in the left ventricles. MMPs localization and activity were also evaluated by in situ zymography. Reactive oxygen species (ROS) were investigated by dihydroethidium (10 μM). Data are presented as mean ± S.E.M. of different experimental n. Two-way ANOVA with Bonferroni correction was used (P < 0.05). Results: SBP values of 2K-1C (165.47 ± 3.98mmHg, n = 12) were increased compared to 2K rats (133.28 ± 2.48mmHg, n = 10; P < 0.0001) in the first week after the surgery. NaHS treatment decreased SBP of 2K-1C NaHS (155.60 ± 5.72mmHg, n = 5) compared to 2K-1C vehicle (202.13 ± 5.57mmHg, n = 7; P = 0.0003). Isovolumetric relaxation time analysis showed increases in values from 2K-1C rats (40.31 ± 2.97ms, n = 7) and NaHS treatment (28.04 ± 1.05ms, n = 5) normalized this parameter (P = 0.0018). 2K-1C rats (2.30 ± 0.11 mm, n = 7) presented increased interventricular septum thickness and NaHS treatment (1.99 ± 0.0 mm, n = 5) reduced this parameter (P = 0.028). MMP-2, Nox2 or Nox4 expression was not different in all groups. The gelatinolytic activity of MMPs was higher in 2K-1C vehicle rats (18,029.31 ± 1,225.42U, n = 3) and NaHS (12,092.70 ± 868.22U, n = 3) reduced it (P = 0.021). In 2K-1C rats (33,868.95 ± 2,103.74U, n = 3), ROS were higher compared to control and NaHS treatment (22,019.50 ± 914.08 U, n = 3) decreased this value (P = 0.0021). Conclusions: Our results showed beneficial effects of NaHS treatment in 2K-1C rats, thus leading to SBP decrease, cardiac function improvement and reduction in both MMPs activity and oxidative stress.