This study has been performed to compare the compartmental modeling of two types of extravascular routes, sustained-release (SR) oral dosage forms and intramuscular (IM) injection. Twenty healthy volunteers received a single dose of 100 mg Diclofenac Sodium (DS) sustained-release tablet, then 75 mg DS Intramuscular injection after two weeks washout period. The concentrations of DS in plasma were measured using reverse-phase high-performance liquid chromatography (HPLC). The data analyzed using compartmental modeling, with single time-variant input and output. Primary kinetic parameters for both formulations, ( , , ) and other kinetic parameters were evaluated. The result shows that the IM injection needs a shorter time to reach the maximum concentration with convergent bioavailability to SR oral dosage forms, in another hand the data of IM injection fitted to single-compartment model with a correlation coefficient of 0.93 and the data of SR tablet fitted to two-compartment models with a correlation coefficient of 0.97.