Stress cardiomyopathy(SCM), is an increasingly recognized clinical syndrome of acute but reversible apical ventricular dysfunction. High levels of epinephrine (Epi) trigger a switch of G protein signaling pathway, from Gs to Gi signaling, producing SCM (Lyon AR, 2008). SCM usually occurs in postmenopausal women, suggesting that the incidence of SCM is associated with the drop in estrogen levels (Kida K et al. 2010). G protein-coupled receptor (GPR30), as a novel estrogen receptor, confers rapid cardioprotection in rat heart.Female Sprague-Dawley (SD) rats (n=6) were anaesthetised with 10% chloral hydrate intraperitoneal injection (3.5ml/kg). Epi was injected via tail vein to establish the SCM model. G1 and G15, as GPR30 agonist and antagonist respectively, were also injected via tail vein. Left ventricular internal diameter at end-systolic dimension (LVIDd), left ventricular internal diameter at end-systolic dimension (LVIDs), ejection fraction (EF) were detected by echocardiography during 4 mins. The expression of p-Akt in hearts was measured. In vitro, the contraction of myocytes (n=6), LDH of supernatant above groups were detected (n=6), Gs protein and activity of Gi protein <span style=”line-height:20.8px”>of cardiomyocytes 2 or G1 pretreatment decreased contraction inhibition induced by Epi(E2: 9.318±0.273 VS. 7.541±0.559,G1:10.08±0.442VS. 7.541±0.559, P<0.05 respectively). However, G15 pretreatment abolished the effect of E2(9.318±0.273 VS. 7.207±0.444, P<0.05). Compared with Normal, Epi increased the LDH concentrations (937.6±27.79 VS. 511.5±48.26, P<0.001). LDH concentrations were declined in E2+Epi, which was abolished by G15 pretreatment(725.7±40.48VS.936.2±27.04, P<0.05). G1 pretreatment decreased LDH concentrations (724.5±55.73 VS. 937.6±27.79, P<0.05). There was no difference in the expressions of Gs protein. The activity of Gi protein increased after stimulated with Epi. Gi protein partly declined when pretreated with E2 or G1 but still higher than Normal group. G15 pretreatment abolished this effect of E2(n=3). These data suggested that activation of GPR30 resisted SCM via down-regulating the activity of Gi/p-Akt signaling pathway.