Abstract: According to a first embodiment, there is provided a sustained-release preparation comprising a water-insoluble or slightly water-soluble polyvalent metal salt of a water-soluble physiologically active substance which is not an endothelin antagonist, and a biodegradable polymer. The sustained-release preparation of the first embodiment is highly efficient in incorporating the water-soluble physiologically active substance and suppresses the initial burst of the water-soluble physiologically active substance. The sustained-release preparation of the present invention is capable of releasing the water-soluble physiologically active substance while retaining its bioactivity after administration in vivo. Furthermore, the water-soluble physiologically active substance in the sustained-release preparation is kept stable for a long period of time, with little loss of bioactivity.