Objective To investigate the effect of xinan nasoyuan fangliu extract on the apoptosis of olfactory neurons in rats with acute sinusitis and the role of the SDF-1/ CXCR4 signaling pathway. Methods Forty Sprague Dawley rats were divided into a control group, model group, treatment group and inhibitor group, with 10 rats in each group. The rats in all groups except the control group were treated with staphylococcus aureus suspension to establish the acute sinusitis model, and the control group received sterile saline. On the seventh day after the model was established, treatment administration was conducted by gavage every day for 1 week continuously. The treatment group was given xin ′an nasoyuan fangliu extract according to body weight ( 7 g / kg), the inhibitor group received 1 mg / kg CXCR4 specific inhibitor AMD3100, and the control group and the model group were given the same amount of normal saline. Pathological features of sinusitis were observed and scored to confirm the establishment of the model. Enzyme-linked immunoassay was used to detect the expression of inflammatory cytokines TNF-α and IL-1β in the olfactory epithelium tissue. TUNEL staining, to detect the number of apoptotic cells, and immunohistochemistry of SDF-1 and CXCR4 were performed in olfactory epithelial tissue of rats in each group. Western blot was used to assess the expression of pro-apoptotic proteins, such as cleaved caspase 3 and Bax, and anti-apoptotic protein Bcl-2 in neurons of the olfactory epithelium. Results The pathological score of sinusitis in the model group was significantly higher than that in the control group (P< 0. 05), and that in the treatment group was significantly lower than that in the model group (P< 0.05). The expression of inflammatory factors in the model group was significantly increased compared with that in the control group (P< 0. 05), and that in the treatment group was significantly lower than that in the model group ( P<0.05). TUNEL staining showed that olfactory epithelial neuron apoptosis increased in the model group compared with the control group (P< 0.05), and was significantly lower in the treatment group and inhibitor group than in the model group (P< 0.05). In the model group, Bcl-2, SDF-1 and CXCR4 expressions were significantly decreased (P< 0.05), whereas cleaved caspase 3 and Bax expressions were significantly increased (P< 0.05) compared with the control group. Bcl-2, SDF-1 and CXCR4 expressions in the treatment group were significantly increased compared with those in the model group (P< 0.05), whereas cleaved caspase 3 and Bax expressions were significantly decreased in the treatment group (P< 0.05). Conclusions Xinan nasoyuan fangliu extract improved apoptosis of rat superior olfactory neurons in acute sinusitis, and the effect may be mediated by inhibition of the SDF-1/ CXCR4 signaling pathway.