Abstract： The present study was aimed to study the effect of hydrogen sulfide (H2S) on rat myocardial ischemia/reperfusion (I/R)injury and whether the effect is mediated by c-Fos protein expression. Male Sprague-Dawley rats were randomly divided into 4 groups:Control group: sham treatment; I/R group: the rat anterior descending branch of left coronary artery was occluded for 30 min and thenreleased to allow reperfusion for 60 min; Naris (exogenous H2S donor) groups: the rats were pretreated with Naris at 2.8 μmol/kg bodyweight and 14 μmol/kg body weight (i.v.), respectively, before I/R treatment. Hemodynamics (LVSP, LV±dp/dtmax) and electrocardio-gram (ECG, lead Ⅱ) were monitored continuously with multi-channel physiological signal analysis system after reperfusion. Myocar-dial infarct size was measured using triphenyltetrazolium chloride (TTC) staining. H2S concentration in the plasma was determinedwith a spectrophotometer. Morphological and ultrastructural changes in myocardial tissue wereevaluated by HE staining and by atransmission electron microscope. The evaluation of c-Fos protein expression in myocardial tissue was performed by immunohistologi-cal staining. The results showed that H2S concentration in rat plasma in I/R group was significantly decreased compared with that in thecontrol group [(30.32±5.26) vs (58.28±7.86) μmol/L, P<0.05]. Naris at 2.8 and 14 μmol/kg body weight reduced the changes in LVSP,LV±dp/dtmax in rat myocardium induced by I/R injury. The values of LVSP, +dp/dtmax and -dpldtmax at 60 min during myocardialreperfusion were enhanced from (75.93±1.10)%, (66.27±4.78)% and (66.01±4.79)% in I/R group to (84.34±2.24)%, (76.38±1.93)% and (75.47±5.29)% in 2.8 μmol/kg body weight Naris group (P<0.05, P<0.01, n=6), (88.40±2.88)%, (80.10±2.09)% and(80.48±6.20)% in 14 μmol/kg body weight NariS group (P<0.01, n=6), respectively. Compared with that in 2.8 μmol/kg body weightNaris group, the enhancing effect was more prominent in 14 μmol/kg body weight Naris group. NariS at 14 μmol/kg body weightmarkedly alleviated the injury in morphological changes and decreased c-Fos protein expression in myocardial tissue compared withthat in I/R group (0.20±0.06 vs 0.32±0.10, P<0.05). These results suggest that H2S protects myocardium against I/R injury and thisprotective effect may be related to the down-regulation of c-Fos protein expression.