Objective: To evaluate the effect of Xuefu Zhuyu Capsule(血府逐瘀胶囊)-containing serum(XFZY-CS) on Eph B4/ephrin B2 and its reverse signal in human microvascular endothelial cell-1(HMEC-1). Methods: XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY-CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on Eph B4/ephrin B2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction, respectively; we also confirmed the results through activating and inhibiting the reverse signal by Eph B4/fc and pyrophosphatase/phosphodiesterase2(PP2). Results: XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesis at the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of Eph B4-m RNA at 12 h(P<0.05), and down-regulates its expression at 24 h(P<0.01). Protein expression of Eph B4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrin B2 increased at 9 h(P<0.05). In addition, 2.5% XFZY-CS played a similar role as the reverse signaling activator Eph B4/Fc ranging from 0.5 to 5 μg/m L(P>0.05). XFZY-CS also reduced the inhibitive effect of PP2 in limited periods. Conclusion: Eph B4/ephrin B2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY’s effect on promoting angiogenesis. Objective: To evaluate the effect of Xuefu Zhuyu Capsule -containing serum (XFZY-CS) on Eph B4 / ephrin B2 and its reverse signal in human microvascular endothelial cell-1 (HMEC- XFZY-CS and the blank control serum were collected. HMEC-1 cells were randomly assigned to 6 groups including the concentration 1.25%, 2.5%, and 5% XFZY-CS groups and their blank serum control ones. The angiogenesis effect of XFZY- CS was tested with an in vitro tube formation assay and the best condition of pro-angiogenesis was determined. The effect of XFZY-CS on Eph B4 / ephrin B2 and the reverse signal were determined by Western blot and real-time quantitative polymerase chain reaction , respectively; we also confirmed the results through activating and inhibiting the reverse signal by Eph B4 / fc and pyrophosphatase / phosphodiesterase2 (PP2). Results: XFZY-CS promoted angiogenesis at the concentration of 2.5% corresponding serum after being cultured for 48 h, while inhibited angiogenesi Under the concentration of 5% after culturing for 48 and 72 h. Under the 2.5% serum concentration, XFZY up-regulated the expression of Eph B4-m RNA at 12 h (P <0.05), and down- regulates its expression at Protein expression of Eph B4 was apparently up-regulated at 12 h and down-regulated at 24 h. The phosphorylation of ephrin B2 increased at 9 h (P <0.05). In addition, 2.5% XFZY CES played a similar role as the reverse signaling activator Eph B4 / Fc ranging from 0.5 to 5 μg / mL (P> 0.05). XFZY-CS also reduced the inhibititive effect of PP2 in limited periods. Conclusion: Eph B4 / ephrin B2 was the upstream signal in the process of angiogenesis and its reverse signaling was responsible for XFZY’s effect on promoting angiogenesis.