Objective To explore the effects of dodecanoylcarnitine （DA） and myristoleic acid （MA） on the function of mouse alveolar epithelial cell line MLE-12 and their underlying mechanisms. Methods An inflammatory model was established by stimulating MLE-12 cells with IL-4. The expression levels of DA， MA， and sphingosine-1-phosphate （S1P） in the cell supernatant were detected by ELISA. MLE-12 cells were separately intervened with DA and MA. RT-PCR and flow cytometry were used to detect the expression changes of inflammatory factors IL-6 and tumor necrosis factor-α （TNF-α） and the level of intracellular reactive oxygen species （ROS）. Additionally， Western blot was performed to detect the expression of key proteins such as p38 mitogen-activated protein kinase （p-38 MAPK） and src homology 2 domain-containing phosphatase 1 （SHP-1）. To explore the role of S1PR2 in the effects of DA and MA， MLE-12 cells were pretreated with the S1PR2 inhibitor JTE-013， and the above experiments were repeated. Results IL-4 stimulation significantly upregulated the levels of DA， MA， and S1P in MLE-12 cells （P<0.05）. DA/MA treatment groups exhibited significantly increased expression of IL-6 and TNF-α compared with the control group （P<0.05）， along with elevated ROS levels （P<0.05）. Western blot analysis revealed that DA/MA promoted SHP-1 dephosphorylation and phosphorylated p38 MAPK activation in MLE-12 cells. Notably， JTE-013 pre-treatment completely reversed these effects （P<0.05）. Conclusion Asthma-related metabolites DA and MA exacerbate the inflammatory and oxidative stress responses of MLE-12 cells by activating the S1PR2 receptor， promoting the dephosphorylation of SHP-1 and the activation of the p-p38 MAPK pathway. This study reveals the core regulatory role of S1PR2 in this pathway as well.