Poly(HEMA-MAA) hydrogel particles were synthesized by redox free-radical polymerization using 2-hydroxyethylmethacrylate, different concentration of methacrylic acid as monomer, ethyleneglycol dimethacrylate as crosslinking agent, and APS/TEMED as free-radical initiator. Fourier transform infrared spectrum of poly(HEMA-MAA) hydrogels showed intense absorption peak of carbonyl group at similar to 1700 cm(-1) due to carboxylic acid groups of MAA, peak at similar to 2960 cm(-1) due to CH stretching and vinylic peak at 1700 cm(-1) independent of MAA concentration. Highest swelling percentage 587% was observed in case of poly(HEMA-MAA) hydrogel synthesized using 30% of MAA while lowest swelling percentage 413% was observed in hydrogel synthesized 10% of MAA at basic pH (8.0). Scanning electron micrograph of copolymeric particles showed the irregular shape of poly(HEMA-MAA) particles with conglomeration with each due to ionization of carboxylic groups. Insulin was radiolabeled using technetium-99m radionuclide and the radiolabeling efficiency was found to be 99%. Poly(HEMA-MAA) hydrogel having 60% of MAA showed the highest insulin loading efficiency of 68% while lowest 37% was observed in case of 10% MAA hydrogel. Insulin release studies showed only 35-65% of insulin was released into the medium from particles at pH 2.5 in 60 min, while insulin release was significantly higher at pH 7.4. Hypoglycemic effect of the 60 and 80 I.U./kg insulin dose loaded in poly(HEMA-MAA) copolymeric particles were carried out in fasted diabetic rats and highest decrease in blood glucose level from 506 mg/dL to 170 mg/dL was observed within first 3 h. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 122: 2004-2012, 2011