The isothermal kinetics of in vitro nicotinamide release from poly(acrylic-co-methacrylic acid) loaded xerogel into water was evaluated. The isothermal kinetics curves of nicotinamide release from poly(acrylic-co-methacrylic acid) xerogel were measured at different temperatures ranging from 296 K to 315 K. It was proven that the kinetics of nicotinamide release from poly(acrylic-co-methacrylic acid) xerogel was a kinetically complex process which was neither controlled by the processes of drug diffusion nor with the relaxation of the xerogel. The kinetic of nicotinamide release from poly(acrylic-co-methacrylic acid) may be described by the kinetics model of reversible first order chemical reaction and the apparent activation energy have value of E-a,E-M=14.1 kJ mol(-1) and preexponential factor ln(A(M) min(-1))=2.3. The rate constants of nicotinamide release ( kR) and the rate constants of its reversible absorption reaction ( kA) were calculated and found to fall within the range 0.019 min(-1)-0.033 min(-1) for kR and 0.014 min(-1)-0.016 min(-1) for kA. The value of activation energy for the nicotinamide releas, E-a.R =21.25 kJ mol(-1), is significantly higher than the value for the process of nicotinamide absorption (E-a,E-A=2.6 kJ mol(-1)). The rate of nicotinamide release was predetermined with the rate of nicotinamide molecules distribution between the hydrogel and surrounding solution. POLYM. ENG. SCI., 55:60-69, 2015. (c) 2014 Society of Plastics Engineers