Abstract A comparative study of the isothermal kinetics of the release of the drug ( E)-4-(4-metoxyphenyl)-4-oxo-2-butenoic acid (MEPBA) from poly(acrylic acid) (PAA) and poly(acrylic-co-methacrylic acid) (PAMA) hydrogel was performed. The isothermal kinetic curves of MEPBA release from the hydrogels in bidistilled water at different temperatures ranging from 20 to 42 °C were determined. The reaction rate constants of MEPBA release were determined using the initial rate, saturation rate and empirical equation developed by Peppas et.al. The so-called “model-fitting method” for determining the kinetics models of both the drug release and absorption of external solution into the hydrogel, was applied. It was found that the kinetics of the MEPBA release both from the PAA and PAMA hydrogels can be best described with the kinetics model of first order chemical reaction. The model's kinetics parameters of the investigated drug release process were calculated and significant differences for the values for PAA and PAMA hydrogels were found. The possibility to describe the kinetics of drug release with the model of reversible chemical reaction of first order was considered. It was found that kinetics of adsorption of the drug's solution can be described with kinetics model of first order chemical reaction for PAMA hydrogel, while for PAA hydrogel it can be described with the kinetics model which is characteristic for the “phase boundary controlled reaction”. Based on the established dependences of the kinetic parameters ( E a and ln A) on the degree of the MEPBA released ( α) as well as on the presence of a compensation effect a new molecular mechanism of drug delivery was established. According to that mechanism, drug release is considered as drug desorption from the xerogel/hydrogel's active desorption centers with different energies. The procedure for determining the distribution function of activation energies was developed. Different activation energy distribution function for PAA and PAMA hydrogels was established.