Aim So far, research on the relationship of mast cells, atherosclerosis and angiogenesis is mostly pathological observation and cytology experiments. Based on the status, compound 48/80 and apolipoprotein E-knockout mice were used to investigate the effect of mast cell degranulation on plaque. Methods 40 apoE-/- mice were fed a Western-type diet from 10 weeks old. At 16 weeks old, mice were divided into 2 groups and treated for 8 days as follows: group 1, mice were intraperitoneal injected with compound 48/80, 0.5 mg/kg, every other day; and group 2, control mice were intraperitoneal injected with buffer. After half an hour of the fouth injection, euthanasia, blood was collected from the orbit for measurement of plasma lipids and tryptase, mice were in situ perfusion fixed with 10% neutral buffered formalin and aortas were removed. Then aortas were fixed in neutral buffered formalin, and embedded in paraffin. Sections were routinely stained with hematoxylin and eosin. Corresponding sections on separate slides were stained immunohistochemically with antibodies against a macrophage-specific antigen (Mac3), α-smooth muscle actin, VE-cadherin. The images were analyzed with a Olympus BX51 microscope and HMIAS2000 software to distinguish the maximum cross section area of aorta plaque and expression of Mac3, α-smooth muscle actin, VE-cadherin between the two groups. Results Tryptase levels were 0.54±0.29 versus 0.36±0.13 mmol/L in the Compound 48/80 and control groups, respectively(p<0.05). There was no difference on serum lipids content. Compound48/80 group were compared with control group,the maximum cross section area of aorta plaque was significantly increased [(1.25±0.36)×10 4 μm 2 VS (0.79±0.24)×10 4 μm 2 in control group, p<0.05],the percent of Mac3+ cell was increased (58.6%±17.3% vs 28.5%±16.4%, p<0.05), the percent of α-smooth muscle actin cell was reduced (36.2%±14.9% vs 69.7%±31.3%, p<0.05) and the MOD of VE-cadherin of aorta endothelium was reduced (48±8 vs 65±10, p<0.05). Conclusions Compound 48/80 promotes mast cell degranulation and increase the maximum cross section area and the percent of Mac3+ cell, reduce the the percent of α-smooth muscle actin cell and the MOD of VE-cadherin of aorta endothelium of aorta plaque.