Objective:To investigate the effects of ERK signaling passway on the class A scavenger receptor(SR-A)-mediated apoptosis in the endoreticulum stessed macrophages. Methods:The expression of phosphorylation of ERK1/2 and GRP78 was measured by Western blot;MTT analysis was used to detect the surviving fraction of RAW264.7 cells treated with different concentrations of PD98059;and apoptosis rates of RAW264.7 cells were observed by flow cytometry after staining of Annexin V FITC/ PI. Results:Fucoidan continuously activated p-ERK,and the expression of p-ERK kept on peak level through 1 to 4 hours,but was low in the SR-A gene knockout macrophages. Under ER stress,fucoidan-induced apoptosis rates of RAW264.7 cells were significantly decreased by PD98059. Conclusion:These results demonstrated that under ER stress,fucoidan could activate the ERK pathway through SR-A;and activation of p-ERK could contribute to the apoptosis of macrophages.