Objective:To investigate the influence of Glaucocalyxin A(GLA)in rats with coronary heart disease(CHD)by regulating protein kinase B(Akt)/nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway.Methods:The CHD rat model was prepared by feeding high-fat diet and intraperitoneal injection of pituitary hormone,and grouped into CHD group,GLA low-dose(GLA-L,5 mg/kg)group,GLA medium-dose(GLA-M,10 mg/kg)group,GLA high-dose(GLA-H,20 mg/kg)group,and GLA-H+LY294002(Akt/Nrf2/HO-1 pathway inhibitor,20 mg/kg GLA-H+40 mg/kg LY294002)group,meantime,10 rats fed with basal diet and intraperitoneally injected with normal saline were used as control group;after the intervention,the serum lipid metabolism levels[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)and triacylglycerol(TG)],vascular en-dothelial function indexes[endothelin-1(ET-1),nitric oxide(NO)],inflammatory factor levels(IL-6,TNF-α),oxidative stress lev-els in cardiac tissue[malondialdehyde(MDA),total antioxidant capacity(T-AOC)],pathological and plaque area changes,and ex-pression levels of Akt/Nrf2/HO-1 pathway-related proteins were measured.Results:Compared with control group,the contents of NO and T-AOC,and the expressions of PI3K,p-Akt/Akt,Nrf2 and HO-1 in the CHD group were greatly decreased,the contents of ET-1,plaque area,MDA,TNF-α,IL-6,TG,TC and LDL-C were greatly increased(P<0.05);compared with CHD group,the contents of NO and T-AOC,and the expressions of PI3K,p-Akt/Akt,Nrf2 and HO-1 in GLA-L group,GLA-M group,GLA-H group were greatly increased,while the contents of ET-1,plaque area,MDA,TNF-α,IL-6,TG,TC and LDL-C were greatly decreased(P<0.05);compared with GLA-H group,the contents of NO and T-AOC,and the expressions of PI3K,p-Akt/Akt,Nrf2 and HO-1 in the GLA-H+LY294002 group were greatly decreased,the contents of ET-1,plaque area,MDA,TNF-α,IL-6,TG,TC and LDL-C were great-ly increased(P<0.05).Conclusion:GLA can inhibit the inflammatory response and oxidative stress level by activating the Akt/Nrf2/HO-1 signaling pathway,and ameliorate the pathological damage and endothelial dysfunction in CHD rats.