Technical Abstract: A series of hydrogel microspheres were prepared from pectin, a hydrophilic biopolymer, and zein, a hydrophobic biopolymer, at varying weight ratios. The hydrogel formulation was conducted in the presence of calcium or other divalent metal ions at room temperature under mild conditions. Studies of the microstructure and the hydration behaviors of the resultant microspheres indicated that the degree of pectin esterification was the controlling factor in determining their stability and capability as a drug delivery system. Pirixicam, an anti-inflammatory drug, was used as a model drug and loaded into the systems in the process of the microsphere formation. Drug loading efficiency was found to be primarily dependant on the ratios between zein and pectin. In comparison with other drug delivery systems prepared from synthetic polymers, the pectin/zein microspheres have several advantages, such as site-specific drug delivery activity and environmentally independent swelling properties, in addition to their biocompatibility, biodegradability, and non-toxicity.