Objective To observe the effect of Yufeng Ningxin Dropping Pills(♂♂♂♂♂♂) on nitroglycerin-induced migraine mice, and explore the effect and mechanism of Yufeng Ningxin Dropping Pills on preventive treatment of vasospasm migraine. Methods Lipopolysaccharide(LPS) was used to stimulate BV2 neuroglial cells, Yufeng Ningxin Dripping Pills(10, 50, 100μmol/L) and puerarin(50 μmol/L) were used for intervention, and cells were collected. Wild-type C57 BL/6 J mice were randomly divided into control group, model group, low-, medium-, and high-dose(200, 360, 600 mg/kg) Yufeng Ningxin Dripping Pill group and puerarin(37.8 mg/kg) group, drugs were given for intervention, migraine model of mice was established with i.p. nitroglycerin solution(10 mg/kg) on 3 rd, 5 th, 7 th, 9 th and 11 th day, hyperalgesia tolerance behavioral experiment(mech. tenderness and heat sensitivity) were started on 3 rd day; After experiment, the serum and brain tissue of mice were taken. The content of reactive oxygen species in BV2 cells of each group was detected; Western blotting was used to detect the expressions of superoxide dismutase 1(SOD1) and SOD2 protein in BV2 cells and calcitonin gene-related peptide(CGRP), c-Fos, phosphorylated extracellular regulated protein kinases(p-ERK) and pro-inflammatory cytokine interleukin-6(IL-6) protein expressions in trigeminal nucleus caudalis(TNC) region in mice of each group; qRT-PCR method was used to detect SOD1, SOD2, IL-1β, tumor necrosis factor-α(TNF-α)m RNA expressions in BV2 cells and IL-1β and TNF-α mRNA expressions in TNC of mice; Immunofluorescence was used to detect the expressions of CGRP and c-Fos in TNC area of mice in each group; Automatic biochem. analyzer was used to detect the alanine aminotransferase(ALT), aspartate aminotransferase(AST) and alk. phosphatase(ALP) activities in serum of mice. Results Yufeng Ningxin Dripping Pills significantly increased antioxidant enzyme SOD1 and SOD2 mRNA and protein expression levels in BV2 cells(P < 0.05, 0.01, 0.001), reduced reactive oxygen species levels(P < 0.01, 0.001), inhibited the inflammatory factor IL-1β and TNF-α mRNA expression(P < 0.001). Compared with control group, basic pain threshold of mice in model group was significantly reduced(P < 0.05, 0.001), expressions of CGRP, c-Fos and p-ERK proteins in TNC area were significantly increased(P < 0.01, 0.001). The expressions of IL-1β, TNF-α mRNA and IL-6 protein in TNC area were significantly increased(P <0.01); Compared with model group, basic pain threshold of mice in each administration group were significantly increased(P < 0.05, 0.01, 0.001), expressions of CGRP, c-Fos and p-ERK proteins in TNC area were significantly reduced(P < 0.05, 0.01, 0.001), expressions of IL-1β, TNF-α mRNA and IL-6 proteins in TNC area were significantly reduced(P < 0.05, 0.01, 0.001), and showed a dose-related relationship; Yufeng Ningxin Dripping Pills had no significant effect on activities of ALT, AST and ALP in serum of migraine mice. Conclusion Yufeng Ningxin Dripping Pills may play a preventive effect on vasospasm migraine by inhibiting vasodilation, inhibiting inflammation and promoting the expression of antioxidant enzymes.