Objective: To explore the roles of Notch signal pathways in propranolol inhibiting hemangioma-derived pericyte(PCs) in order to improve the therapeutic mechanism of propranolol and provide new targets for its clinical treatment. Methods: The specimens of proliferative hemangioma were obtained from operation. Cell suspension was prepared after incubation and digestion. Then a-SMA positive PCs were sorted out by flow cytometry and sub-cultured. Propranolol in different concentrations (0, 10, 20, 40, 80, 160, 320 μmol/L) was added into PCs solution and cultured for 24, 48 and 72 h respectively. And CCK-8 culture and BrdU labeling solutions were added. Activity and proliferation of PCs before and after intervention of propranolol were respectively tested. The level of mRNA of Notch3 and Hes1 in PCs before and after intervention of propranolol were detected by RT-PCR. All data were analyzed by SPSS 13.0 statistical software. Single factor analysis of variance and paired data t test were used. Results: The rate of a-SMA positive cells was 98.0%. The longer incubation time, the more marked inhibitions of cell activity and proliferation after propranolol dosing. The inhibition of cell activity and proliferation were significant at a propranolol concentration of 40 μmol/L. Experimental group of cell activity(0.17±0.05) is compared to control group(0.53±0.03) with paired data t test, t value=3.502. Similarly, experimental group of cell proliferation(301.66±28.71) is compared to control group(498.66±56.09) with paired data t test, t value=7.425.And significant differences existed between them and those of control group (P<0.05), especially at 72 h. Gene expressions of Notch3 and Hes1 increased with rising propranolol concentrations. Conclusions One therapeutic mechanism of propranolol to infantile hemangioma may be achieved by pericytes. Propranolol can inhibit the growth of infantile hemangioma by inhibiting proliferation of pericytes which is closely related to activated Notch signal pathways.