The oxidative behavior of diclofenac sodium (DCF) has been investigated by cyclic voltammetric and differential pulse voltammetric techniques, using a Tyrosine-modified carbon paste electrode (TCPE). Cyclic voltammetry was used to study the influence of pH on the anodic peak current of DCF. The solution conditions and operating parameters were optimized. The phosphate buffer (PBS) of pH 7.0 was selected as a suitable analytical medium in which DCF exhibited a sensitive diffusion-controlled oxidative peak at 0.67 V (vs Ag/AgCl). The peak current varied linearly with DCF concentration in the range between 10 mu M and 140 mu M with a detection limit of 3.28 mu M. The applicability of the proposed method was illustrated by the determination of DCF present in pharmaceutical samples and human urine samples. A mean recovery of DCF in the tablet was 99.5%, with a relative standard deviation of 1.15%.