The present study was focused on the assessment of Catalase (CAT) and Acetylcholinesterase (AChE) activities in Mediterranean clams (Ruditapes decussatus) exposed to 50, 100 and 150 μg/L of Permethrin for 5, 10, 15, 20 and 25 days. In water, the measured concentrations of Permethrin in the treated aquariums were respectively 16.66, 38.24 and 55.61 μg/L. Results showed that CAT activity was increased after 5 days of exposure to high concentration reaching maximum value of 10.14 μmol/min/mg proteins after 25 days. However, no significant changes in AChE activity after 5 days of exposure were detected in all treated groups. AChE activity was significantly inhibited after 10 days with 100 and 150 μg/L and still depending on concentration and time. Maximum inhibition of AChE activity was reached after 25 days with the highest concentration of Permethrin. Our data indicated that exposure to Permethrin modifies biomarker profiles inducing oxidative stress and reducing AChE activity in Mediterranean clams.