Objective: To investigate the effect of liposomal clodronate(LC) on lung injury secondary to severe acute pancreatitis (SAP) in rats and its relations with Aktand MAPK (ERK1/2) pathways. Methods: Forty-eight SD rats were equally randomized into sham operation group, SAP model group (model group) and SAP model plus LC treatment group (LC group), and in the latter two groups, SAP model was created by injection of 5% sodium taurocholate beneath the pancreatic capsule, and after that were given naked liposome and LC respectively by tail vein injection. In each group at 2 and 6 h after operation, the serum levels of amylase (AMS), IL-6, and TNF-αwere measured, and pathological changes, as well as Akt and MAPK (ERK1/2) expressions in the lung tissue were observed. Results: In both model group and LC group compared with sham operation group, the serum levels of AMS, IL-6 and TNF-α,the pathological score, and the expression levels of Akt and MAPK (ERK1/2) were significantly increased, and all became evident as time went on (all P<0.05), but all above parameters in LC group were significantly lower than those in model group at each time point (all P<0.05). Conclusion: LC has alleviative effect against SAP-induced lung injury in rats, and the mechanism may be associated with reduced inflammatory factors that result from inhibition of Akt and MAPK (ERK1/2) signaling pathways after LC uptake by alveolar macrophages.