Objective: To analyse characteristics of pseudoallergic reactions (PARs) of Shuanghuanglian injection (SHLI) and investigate impact of injection speed on PARs. Method: ICR mice were divided into negative group (saline)

positive group (histamine of 10 mg·kg-1) and low (150 mg·kg-1)

medium (300 mg·kg-1)

high (600 mg·kg-1) doses of SHLI.Mice received test articles containing 0.4% Evans blue(EB) by tail intravenous injection

after 30 minutes of administration

area of blue staining and incidence of hypermeability on auricle were recorded

EB exudation of ears was quantitative measurement.ICR mice were randomly divided into negative group and SHLI group of 600 mg·kg-1

mice in different groups were given test articles without EB by tail intravenous injection.After 30 minutes

concentrations of histamine

vascular endothelial growth factor (VEGF)

tumor necrosis factor-α(TNF-α) in plasma were measured by ELISA kit

lung and both ears were taken for histopathology evaluation. Result: Both reaction incidence and degree of vascular hyperpermeability were higher with increasing of SHLI dosage.Concentrations of histamine and VEGF were increased significantly after intravenous administration of SHLI

while the concentration of TNF-α was no significant difference.Histopathology evaluation showed edema

neutrophil infiltration in auricle and lung of SHLI groups.And injection speed of SHLI had influence on extent of PARs.When the same dose of SHLI were administrated by intravenous injection

injection at the lower speed (60

120 s) could cause lighter PARs by comparing with injection speed of 5 s. Conclusion: SHLI may induce vascular hyperpemeability so as to cause PARs in mice.PARs induced by SHLI may be associated with release of histamine and VEGF.SHLI-induced PARs shows a relationship with dose and injection speed.The higher dose and higher injection speed can increase incidence and degreed of PARs.Control of dose and injection speed is important to reducing PARs of SHLI.