The release of hemoglobin from hydrogel matrices of polyethylene glycol (PEG), polyvinyl alcohol (PVA), and crosslinked polyacrylamide (PAM) was investigated in phosphate-buffered saline (PBS, pH 7.4) as a release medium. The hemoglobin was loaded onto hyrogels by swelling them in hemoglobin solution and the effect of composition of the hydrogel on the amount of hemoglobin loaded was observed. The effects of experimental parameters such as varying concentrations of PEG, PVA, PAM, and crosslinking agent in the feed mixture. pH of the release medium, and the presence of salts were investigated on the release dynamics of the hemoglobin, The release results were analyzed on the basis of the kinetic data. and the kinetic parameters such as the diffusional exponent (n) and diffusion constant (D) were evaluated. From the kinetic parameters data an attempt was made to explore the nature of the mechanism of the hemoglobin release process.