The surface of albumin microspheres could be modified with methotrexate (MTX) by using 1,3-dicyclohexylcarbodiimide (DCC). Surface-modified albumin microspheres entrapping no MTX (SAMS), free MTX (SAMSF) and MTX-bovine serum albumin (BSA) conjugates (SAMSC) were prepared. respectively, and their release characteristics were investigated in the presence of trypsin using a dissolution tester. The mean diameters of all the microspheres were $5{sim}8;{mu}m$, and their shapes was small and uniform. MTX bound tn their surfaces was released slower than the entrapped free MTX, and laster than the entrapped MTX-BSA conjugates. Also, surface-modified MTX was scarcely released in the absence of a proteolytic enzyme. Therefore, the surface-modified MTX may be released rapidly from SAMSC at the target site, and thereafter MTX may be released slowly from the encapsulated MTX-BSA conjugates in SAMSC for a long period.