Backgrounds: Oral propranolol has recently been shown to be highly effective for infantile hemangiomas (IHs), and is currently recommended as the first-line treatment of IHs. The present prospective study aimed to identify possible therapeutic mechanisms of propranolol and early regression indicators with hematological parameters. Materials and Methods: Seventy-five blood samples were obtained from 30 patients with IH (median age of 80 days, range between 36 days and 265 days) who were treated with propranolol in 11 medical centers in Korea. Twelve different serum cytokines involving angiogenesis, vasculogenesis and/or chronic inflammation were analyzed at 0, 1 and/or 12 months after propranolol treatment using Luminex Multiplex Assays. Results: Sixteen patients completed the study with 3 blood samples at 0, 1 and 12 months and 7 patients showed excellent regression with visual analogue score (VAS) of ＞8 (maximum score of 9). Seven patients were lost their follow-up or withdrew their consent to the study after ＞1 month of propranolol treatment and 7 patients are still under the study. Patients with larger size of hemangioma showed significantly higher platelet-derived growth factor-BB ( PDGF-BB) (r=0.38, p=0.05) and vascular endothelial growth factor-alpha (VEGF-α) (r=0.40, p=0.04). Serum VEGF-α showed steady decrease over treatment period with statistical significance (p=0.01). Serum matrix metalloproteinase-2 (MMP-2) and VEGF-α at 1 month were negatively correlated with improvement of hemangioma at 1 month (r=-0,43, p=0.03 and r=-0.38, p=0.04, respectivaly). Patients with greater improvement of hemangioma at 1 year showed significantly lower 1 month- monocyte chemoattractant protein-1 (MCP-1) (r=-0.64, p0.01) and interleukin-2 (IL-2) (r=-0.577, p=0.02). Conclusion: In the present study we show for the first time the significant change of several blood parameters as serum indicators of IH regression and potentially useful signs to monitor vascular growth.