To explore the effect of low molecular weight fucoidan (LMWF) on renal ischemia-reperfusion injury (RIRI) and its mechanism.We studied the effects of LMWF in vivo using a RIR model.Kidneys from mice that underwent IR showed characteristic morphological changes, such as tubular dilatation, and loss of brush border, with renal dysfunction which was demonstrated by increased serum creatinine and BUN concentration.In vitro, we used CoCl2-induced hypoxic model and hypoxia-reoxygenation injury model which is known to mirror the response obtained in animal models of IR.LMWF treatment protected kidney against renal damage induced by IR in mice.LMWF suppressed activation of MAPK, which consequently resulted in a significant decrease in the expression of cyto-c, Bax/Bcl-2 and cleaved caspase 3/caspase 3 ratios, phosphorylation of p53.In accordance with these biochemical changes,the histologic evaluation of the tissues revealed that LMWF was effective at protecting the kidneys against IR, and that this protective effect led to the restoration of renal function and balance of oxidative stress and antioxidative defense.In vitro we also investigated the effect of LMWF on cells subjected to chemical hypoxia or hypoxia-reoxygenation, and the intracelhlar signaling pathways in HK2 cells.Pretreatment of HK-2 cells with LMWF1-20 g·ml-1 alleviated both the CoCl2-induced and hypoxia-reoxygenation induced loss of cell viability and dissipation of ΔΨm.LMWF also inhibited activation of MAPK, which resulted in a significant decrease in the expression of cyto-c, Bax/Bcl-2 and cleaved caspase 3/caspase 3 ratios, and reduced pbosphorylation of p53 in a dose-dependent manner.In conclusion, our results firstly indicated LMWF ameliorates acute RIRI via suppressing MAPK signaling pathway in vivo and in vitro,which suggests that LMWF may serve as an potential therapeutic agent for the treatment of acute RIRI.