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Our purpose was to develop and characterize a protein drug delivery system in agarose-glucan complex. The complex was produced by sonicating the mixture of agarose-glucan components and a protein in liquid paraffin with Sonics Vibracell Processor adapted from method of Nuo Wang et all 1997 . We used etanercept, an anti-tumor necrosis factor-alpha (TNF-α) as a model protein drug, which was encapsulated successfully into agarose-glucan complex system. This protein can neutralize the TNF-α, a pro-inflammatory cytokines that plays a pivotal role in regulating the inflammatory response in rheumatoid arthritis (RA) and well known as mediator worsening RA pathogenesis. The agarose-glucan complex we made possessed a range of sizes from 30 to 150 nm, dissolving well within a range of pH buffer from 5.2 to 6.2, an average protein encapsulated efficiency up to 70%, and protein release efficiency of 50% after 24 hours. This research is the base for developing nanogel-size targeted drug delivery in RA treatment.