The effects of herbicide pollution on the marine environment and aquatic product quality and safety has been of great concern. To explore the effects of metolachlor pollution on shellfish cultivation in the Yellow River Delta, the effects of different mass metolachlor concentrations on gill and hepatopancreas antioxidant enzyme activities and tissue structure of Mactra veneriformis were investigated. Additionally, the tissues at different times during the exposure and elimination phases were determined. Superoxide dismutase (SOD), catalase (CAT) activity, variations in malondialdehyde (MDA) content, and changes to the microstructure of tissues were observed. The results showed that metolachlor induced or inhibited anti-oxidase activity under differing metolachlor concentrations. It was found that 10 μg/L of metolachlor significantly increased SOD activity in gill tissue, and different concentrations of metolachlor inhibited CAT activity in the gill and hepatopancreas. Metolachlor at 0.5 and 2.5 μg/L caused irreversible oxidative damage to SOD and CAT in the gills; the SOD and CAT activities in the gills of the 10 μg/L metolachlor concentration group was restored to the level of the control group during the elimination phase. The SOD and CAT activities in the hepatopancreas of the three concentrations groups were restored to or close to the level of the control group during elimination phase. Compared with SOD, the CAT activity was more susceptible to exogenous stimulation and was inhibited; this may be related to the sensitivity and mechanism of action of the two enzymes. After eliminating drug stress, the MDA content in the gills and hepatopancreas of all concentration groups had returned to or was lower than that of the control group. This suggests that the effects of metolachlor stress on lipid peroxidation in the gills and hepatopancreas of Mactra veneriformis may be reversible. Metolachlor stress induced gill filament enlargement, ciliary shedding, epithelial cell damage, and digestive canal damage; the dose-time effect of two types of tissue damage was evident. However, the effect of drug stress on antioxidant enzymes in tissues did not exhibit a significant dose-effect; this does not correspond to tissue structure damage. It is speculated that there was insufficient damage caused by drug stress to breakdown the antioxidant enzyme system. Different concentrations of drug stress activated various antioxidant enzymes to maintain the physiological balance of the body; this aspect requires further investigation. The results of this study offers a reference for the risk assessment of marine ecosystems and and achieving a controllable level of quality in shellfish aquaculture in tidal areas.