P‑selectin, an integral membrane glycoprotein of platelets and endothelial cells, and the soluble form of P‑selectin are hypothesized to play a role in the initiation of atherosclerosis and acute myocardial infarction (AMI). However, limited data are available with which to evaluate the main role of soluble P‑selectin (sP‑selectin) in the onset or the severity of AMI. In the present study, we investigated 15 patients who suffered from angina, 10 patients who underwent percutaneous coronary intervention (PCI) therapy and 10 patients who underwent thrombolysis therapy, compared with 15 volunteers with no cardiovascular disease. We confirmed that the plasma sP‑selectin levels were increased in patients with obesity (particularly pericardial obesity) and hyperlipidemia, positively correlated with plasma tumor necrosis factor (TNF)‑α and strongly negatively correlated with adiponectin in all patients regardless of AMI status. Furthermore, sP‑selectin levels were significantly higher in PCI and thrombolysis patients compared with angina patients and the control cohort. However, we observed that sP‑selectin levels did not change following PCI and thrombolysis therapy. In addition, there was no correlation between sP‑selectin levels and the severity of AMI in the cohort which received PCI or thrombolysis therapy. Therefore, we deduced that sP‑selectin only induced the onset of AMI but did not promote its severity. To confirm this hypothesis, a P‑selectin inhibitor was administered to an atherosclerosis formation model, plaque rapture model and neointimal hyperplasia model. We revealed that atherosclerotic plaque formation and rupture, neointimal formation and neointimal bleeding were suppressed by the sP‑selectin inhibitor. We concluded that sP‑selectin, induced by systemic inflammation in conditions including obesity and hyperlipidemia, promoted atherosclerotic plaque and neointimal formation, plaque rapture and neointimal bleeding, further leading to AMI. We also demonstrated that sP‑selectin had no effect on the severity of AMI.