Objective To observe the protective effect of mogroside V against acute lung injury in rats with meconium aspiration syndrome (MAS) and to explore its possible mechanism. Methods Forty-eight healthy Wistar rats were randomly divided into sham operation, model, low-, medium- and high-dose mogroside V groups (2. 5, 5 and 10 mg /kg) and a dexamethasone group (0. 5 mg / kg) with eight mice per group. MAS models were established by oral tracheal intubation. After modeling, low-, medium- and high-dose mogroside V groups, and the dexamethasone group were administered the indicated doses of drugs, whereas model and sham operation groups were administered the same volume of normal saline. Pathological changes of lung tissues were observed by HE staining. The wet-to-dry weight ratio (W/ D) of lung tissues was calculated. The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β in serum and bronchoalveolar lavage fluid were measured by ELISA. Malondialdehyde ( MDA) and activity of superoxide dismutase (SOD) in lung tissues were detected by colorimetry. Protein expression of c-Jun N-terminal kinase ( JNK) and phosphorylated JNK (p-JNK) in lung tissues was detected by Western blot. Results Compared with the sham operation group, the pathological score of lung tissues and W/ D were increased (P<0. 05), TNF-α, IL-6 and IL-1β levels were increased in bronchoalveolar lavage fluid and serum (P<0. 05), MDA and MPO were increased in lung tissues, the SOD level was decreased (P<0. 05), and p-JNK protein expression in lung tissues was upregulated in the model group (P<0. 05). Compared with the model group, the pathological score of lung tissues and W/ D were decreased ( P< 0. 05),TNF-α, IL-6 and IL-1β levels were decreased in bronchoalveolar lavage fluid and serum (P<0. 05), MDA and MPO were decreased in lung tissues, while the SOD level was increased in medium- and high-dose mogroside V groups, and the dexamethasone group (P<0. 05). p-JNK protein expression was downregulated in lung tissues in medium- and high-dose mogroside V groups (P<0. 05). Conclusions Mogroside V may reduce inflammatory and oxidative stress damage in MAS rats by inhibiting JNK phosphorylation and thus protect them against acute lung injury.