In order to detect physiological mechanism and the changes of histological structure with the abrupt decline in salinity in Manila clam, Ruditapes philippenarum, effects of abrupt decreasing in salinity on the activity of three antioxidant enzymes (SOD, GSH-PX, CAT) in hemolymph of R. philippenarum were studied. The clams were reared in different salinity of 35 (the control group), 25 and 15 and sampled at 2, 6, 12, 24, 36, 48, 60 h. In both low-salinity groups, the activity of the SOD and GSH-PX was higher than that in control group (P<0.05) at the beginning, then decreased significantly and tended to be stable at the end of experiment. In group of salinity 25 and 15, the activity of SOD increased significantly and lasted for 48 h and 12 h before the decrement (P<0.05). The time of increasing and decreasing of activity of GSH-PX were roughly the same in group of salinity 25 and 15. The activity of CAT was decreased gently with a slight increase 6 h (P<0.05). The activities of the three antioxidant enzymes were returned to the levels of controls, which showed that the clams had high resistance against changes of salinity, and could regulate the activity of the antioxidant enzymes to adapt to the low salinity. Tissue sections, which sampled from clams suffered 6 days low salinity stress of 15, showed that the fill filament connections and the arrangement were damaged, epithelial folds were disappeared. The heights of acinic cells in hepatopancreas reduced, the cytoplasm was not rich and the acinar lumens were enlarged. The epithelial folds were reduced and the mucous cells were rich in mantle and meaty siphon during low-salinity rearing. These results would be an important basis of the studies on physiological ecology during changes of salinity in clams.