Stability and disintegration of natural polyelectrolyte complex microspheres for protein drugs delivery have been extensively investigated because of their great influence on the drug release patterns. In this study, we tested stability of microspheres with alginate (Alg) core layered by either chitosan (Chi) or glycol chitosan (GChi) by examining release profiles of fluorophorelabeled bovine serum albumin (BSA) and lysozyme (Lys) from the microspheres. While GChi shell was disintegrated quickly, Chi-shell microspheres showed good stability in PBS. Disintegration of the coated layer induced the core material instable. The results indicated that while the charges of the shell material provided additional diffusion barrier against the protein release, the key factor to hold the proteins inside the microspheres was the integrity of the outer coating layer.