Abstract：Objective：To observe the effects of Icariin (ICA) on ventricular remodeling in rats with heart failure with preserved ejection fraction (HFPEF) through nitric oxide (NO) - cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Methods： Deoxycorticosterone acetate (DOCA)- sensitive HFPEF rat models of were established，and were randomly divided into the model group，the low-dose， medium- dose and high- dose of ICA groups， and the inhibitor group； a total of 12 rats were randomly selected as the control group. Each group was given the gastric irrigation with corresponding medicines once a day for 6 weeks. The heart function of rats was detected by echocardiography； hemodynamic parameters were measured by cardiac catheterization procedure； the pathological injury of myocardium was observed by HE staining；the levels of NO，cGMP，reactive oxygen species (ROS)，interleukin (IL)- 6，IL-1β，and tumor necrosis factor (TNF)-α were detected by reagent kit；the expressions of plateletendothelial cell adhesion molecule- 1 (CD31) were observed by immunofluorescence staining； the expressions of PKG，endothelial nitric oxide synthase (eNOS)，inducable nitric oxide synthase (iNOS)，and soluble guanylate cyclase α (sGCα) were detected by Western blot. Results：When compared with those in the control group，the levels of LVEF，LVFS，E/A，LVSP，+dp/dt max，-dp/dt max，NO，and cGMP， CD31，and the protein expression levels of PKG，eNOS and sGCα in the model group were decreased (P＜ 0.05)；the levels of LVAM，LVPW，LVEDD，LVESD，LVEDP，ROS，IL- 6，IL- 1β，and TNF- α，and iNOS protein expression levels in the model group were increased (P＜0.05). When compared with those in the model group，the levels of LVEF，LVFS，E/A，LVSP，+ dp/dt max，- dp/dt max，NO，and cGMP， CD31，and the protein expression levels of PKG，eNOS and sGCα in the low- dose，medium- dose and high- dose of ICA groups were increased (P＜0.05)； the levels of LVAM， LVPW， LVEDD， LVESD， LVEDP，ROS，IL-6，IL-1β，and TNF-α，and iNOS protein expression level in the low-dose，mediumdose and high- dose of ICA groups were decreased (P＜0.05)； the changes were more significant in the high-dose of ICA group (P＜0.05). When compared with those in the high-dose of ICA group，the levels of LVEF， LVFS， E/A， LVSP， + dp/dt max， - dp/dt max， NO， and cGMP， CD31， and the protein expression levels of PKG，eNOS and sGCα in the inhibitor group were decreased (P＜0.05)；the expression level levels of LVAM，LVPW，LVEDD，LVESD，LVEDP，ROS，IL- 6，IL- 1β，and TNF- α，and iNOS protein in the inhibitor group were increased (P＜0.05). Conclusion： ICA can reduce inflammation and improve ventricular remodeling by activating NO-cGMP-PKG pathway.