FIELD : medicine; pharmaceuticals.SUBSTANCE : group of inventions relates to pharmacy, in particular to microspheres for controlled release of protein and methods for production thereof. Microsphere contains a biodegradable polymer selected from a group consisting of polylactide; polyglycolide; poly(d, 1-lactide-co-glycolide); polycaprolactone; polyorthoester; copolymer of polyether and polyether; and polylactide and polyethylene glycol copolymer; and a protein mixture selected from a group consisting of : protein-polyethylene glycol conjugate and hydrophobic anion of organic acid; protein and hydrophobic anion of organic acid; combinations thereof, wherein the organic acid includes pamoic acid, dioctyl sulphosuccinic acid, furoic acid or mixtures thereof; and where the microsphere is formed by a method comprising : adding an organic acid to a protein-polyethylene glycol or protein conjugate in a water-immiscible solvent in an organic phase to form a water-immiscible solution, wherein addition takes place without presence of water. Also disclosed is a method of producing a salt of a protein-polyethylene glycol conjugate with high hydrophobicity and a method of producing a microsphere which provides controlled release of an active agent which contains a salt of a protein-polyethylene glycol conjugate. This method involves preparing an aqueous protein solution. Aqueous protein solution contains protein and a buffer solution providing a certain pH. Method also involves reacting polyethylene glycol with protein to form a protein-polyethylene glycol conjugate. Method also includes protonation of amino group in protein-polyethylene glycol conjugate due to hydrophobic organic acid in organic phase. As a result of said protonation, a salt of a protein-polyethylene glycol conjugate is formed, which contains a hydrophobic anion, which increases hydrophobicity of the salt of the protein-polyethylene glycol conjugate.EFFECT : group of inventions provides preparing drug preparations with a constant profile of protein release.40 cl, 11 dwg, 2 tbl, 14 ex