Epidemiological and toxicological studies have demonstrated that exposure to fine particulate matter (PM2.5) during pregnancy is harmful to the tissues of the offspring. However, the mechanism by which PM2.5 exposure causes lung damage in the offspring or potential dietary therapy for this condition remains unclear. Mogrosides (MGs) are derived from the traditional plant Siraitia grosvenorii and are used medicinally, where they can moisten the lungs and relieve coughing. In this study, pregnant rats were exposed to PM2.5 by intratracheal instillation and treated with MGs by gavage to model the effect of PM2.5 in the offspring and the interventional effect of MGs on lung tissue. We then used transcriptomics, metabolomics, and RT-qPCR as tools to look for metabolite and genetic changes in the offspring. We found that when compared to the control group, the mRNA levels of the inflammatory mediator Pla2g2d and the metabolites lysophosphatidylcholines (LysoPCs) and arachidonic acid (AA) were up-regulated in the lung tissues of PM2.5 group. In contrast, these inflammatory changes were restored after treatment with MGs during pregnancy. In addition, the levels of AA, LPC 15:0 and LPC 18:0 were elevated in the PM2.5 group compared with control group. This increase was inhibited by co-administration of MGs. The change of PGA1 was adverse. In conclusion, even a relatively low exposure to PM2.5 in rats during pregnancy produces inflammation in the lungs of the male offspring, and an intervention with MGs could significantly alleviate this effect. Furthermore, Pla2g2d may represent a potential target for MGs resulting in the improvement of PM2.5-induced lung injury.