Water-soluble Mn2+-doped ZnSe quantum dots (QDs) were synthesized using a hydrothermal method. The characteristics of the precursor solutions greatly affected the photoluminescence (PL) properties of the ZnSe:Mn QDs. In QDs synthesized with alkaline precursor solutions, a PL band originating from the intra-3d shell transition of Mn2+ is clearly observed, indicating that Mn2+ ions are thoroughly doped inside the ZnSe QDs. The PL quantum yield of the ZnSe:Mn QDs synthesized under the optimum conditions reached 20%. By introducing a ZnS shell at the surface of the ZnS:Mn QDs, the PL properties were improved and the PL quantum yield was further increased to 30%.