Aim DL08052 is a novel Rhokinases inhibitor which has been found to have potent cardiovascular effects.In the present research, we aimed to study the potential of DL08052 in the treatment of pulmonary arterial hypertension (PAH) and discuss the underlying mechanisms preliminarily.Methods A classical PAH animal model was used, which was established by single injection of 50 mg · kg1 monocrotaline (MCT).One week later,the rats were administrated with 1,3, 10 mg · kg1 DL08052 via intraperitoneal injection for 18 days.At the end of the experiment, the body weight and survival rate were recorded.Meanwhile, the respiration function, heart function, blood pressure and pulmonary artery pressure were detected.Serum was collected for biochemical index analysis.The weight of vital organs was used to calculate the organ index.Histopathology examination was employed to observe the subtle changes in hearts, vessels and lungs.Furthermore, the mechanisms were studied mainly by the method of western blotting.Results DL08052 did not show significant influence on body weight of PAH rats.But the survival rate of PAH rats treated with 3 and 10 mg · kg1 DL08052 was increased up to 90.9% compared with the model group (68.2%).DL08052 improved the pulmonary artery blood flow especially the maximal velocity (PV max) from 397.2 cm · s1 to 506.5,540.1 and 574.0 cm · s1 respectively.The results of echocardiography and electrocardiogram show that DL08052 had little effect on left ventricle and systemic circulation but attenuated right ventricle injury and decreased the right ventricle pressure from 73.73 mmHg to 47.80, 42.64 and46.45 mmHg respectively after DL08052 intervention.Disease markers of PAH including NTproBNP in serum and ET1 in lung tissue homogenate and serum biochemical indicators, ALT, AST and LDH, were reduced by DL08052.DL08052 also relieved edema of lungs and decreased inflammatory cytokines production.Through the examination on histopathologic slide of pulmonary main artery, right ventricle and lung, DL0805 derivatives were found to have significant protection effect on structural changes of organs induced by pulmonary hypertension.According to the preliminary study on the mechanisms of DL08052 in PAH, Rho/ROCK pathway was significantly inhibited by DL0805 derivatives.In addition, DL0805 derivatives showed effect on BMPRⅡ/pSmad pathway and apoptosis related pathway.Conclusion DL08052 has showed potent treatment effect on the PAH rats.And the underlying mechanisms studies also indicated that RhoA/ROCK and BMPRⅡ pathways were involved.This work will provide basis experimental data for the further research and development of DL08052.