A major concern in developing protein-based biopharmaceuticals is protein instability. A strategy with the use of reducing agent pretreatment to improve protein stability was developed for recombinant hCD83ext (i.e. the extracellular domain of human CD83) with a potential therapeutic activity. Under physiological conditions, the therapeutic product tended to denature, form aggregates and precipitates, and eventually degrade. The reducing agent pretreatment was demonstrated to be effective in improving the protein stability.