Objectives Our aim was to verify the alleviation effect of sphingosine-1-phosphate (S1P) in a miniature pig model. Material and methods Thirty male miniature pigs were randomly separated into 10 groups in our experiment. We administered S1P through the parotid duct in a retrograde fashion 2 hr before irradiation (IR). The salivary flow rate and blood flow rate were tested 20 weeks after IR. The apoptotic level was checked at 12, 24 hr and 7 days post-IR. Results Twenty weeks after IR, the salivary flow rate of the IR-side parotid gland in IR + S1P group can be maintained at about 40% of the non-IR side, while only 20% was maintained in the IR group. The blood flow rate and microvascular density were significantly higher in the IR + S1P group than in the IR group. The apoptotic level and cleaved caspase-3 expression were downregulated in IR + S1P group, and the ratio of Bcl-2/Bax was increased. The blood flow rate and CD31 level were significantly restored at 12, 24 hr and 7 days post-IR. Conclusion Sphingosine-1-phosphate may partially alleviate IR-induced parotid dysfunction by decreasing apoptosis of microvascular endothelial cells and maintaining the blood flow rate.