Objective To explore the possible mechanisms of protective effect of simvastatin on acute pulmonary embolism(APE) in rat. Methods Seventy-two male Sprague-Dawley rats were randomly divided into sham-operation group, pulmonary thromboembolism(PTE) group and statins intervention group(n = 24 in each group). Right ventricular systolic pressure(RVSP) and mean pulmonary arterial pressure (mPAP) were measured by right heart catheter at 2 h, 6 h, 24 h after induction of PTE. Blood gas analysis was processed and immunohistochemical analysis was performed to study the changes of endothelial nitric oxide synthase leNOS in pulmonary vascellum at 6 h following induction of PTE. ELISA kits were used to evaluate the level of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in plasma. Results MPAP and RVSP at each time point was increased in the PTE group compared with sham-operation group(P＜0.01) and decreased in the statins intervention group compared with PTE group significantly(P＜0.05). Compared with PTE group, PaO2 in statins intervention group was increased significantly 6 h after induction of PTE(P＜0.05). Compared with sham-operation group, eNOS protein expression in PTE group at 6h after induction was decreased significantly(P＜0.01). Compared with PTE group, it increased significantly in statin group(P＜0.05). Compared with sham-operation group, the plasma levels of IL-6 and TNF-α at each time point in the PTE group were increased slightly(P＞0.05), while decreased slightly with simavastatin pretreatment(P＞0.05). Conclusion Pretreatment with simavastatin decreases RVSP and mPAP, and improves hypoxemia and endothelial function in the rats with PTE, while has no effect on IL-6 and TNF-α.