Endothelial microparticles (EMPs) are complex vesicular structures with great significance in vascular pathophysiology. Here, we aimed to determine the impact of therapeutic drugs for infantile hemangioma, a common vascular tumor of infancy, on the biochemical features of EMPs. We exposed human umbilical vein endothelial cells to propranolol (Pro), dexamethasone (Dex), or rapamycin (Rap). Compared with controls, Pro and Rap dramatically augmented EMP release, whereas Dex significantly suppressed EMP generation. Drug-stimulated EMPs could inherit but tended to lose specific endothelial surface antigens from their parental cells. On the one hand, markedly distinct messenger RNA expression patterns were observed within and between drug-stimulated endothelial cells and derived EMPs. On the other hand, Rap-treated endothelial cells and Pro-induced EMPs displayed downregulation of multiple angiogenesis-related molecules at messenger RNA level compared with corresponding controls. Meanwhile, among tested angiogenesis-associated microRNAs, twelve microRNAs were downregulated in drug-induced EMPs, whereas only let-7b and miR-133a were markedly upregulated. Collectively, these data may indicate selective and distinctive package of biomolecules into EMPs depending on specific drugs. Our findings may provide novel insights into the underlying mechanisms of pharmacological therapy for infantile hemangioma.