In this study, a series of poly(lactic-co-glycolic acid) (PLGA) microspheres with different particle sizes for arterial embolization surgery were prepared. The polydopamine (PDA) and polydopamine/polyethyleneimine (PDA/PEI) were respectively coated on the PLGA microspheres as shells, in order to improve the hydrophilicity and dispersibility of PLGA embolization microspheres. After modification, with the introduction of PDA and PEI, many hydrophilic hydroxyl and amine groups appeared on the surface of the PLGA@PDA and PLGA@PDA/PEI microspheres. SEM images showed the morphologies, sizes, and changes of the as-prepared microspheres. Meanwhile, the XPS and FT-IR spectra demonstrated the successful modification of the PDA and PEI. Water contact angles (WCAs) of the PLGA@PDA and PLGA@PDA/PEI microspheres became smaller, indicating a certain improvement in surface hydrophilicity. In addition, the results of in vitro cytotoxicity showed that modification had little effect on the biosafety of the microspheres. The modified PLGA microspheres suggest a promising prospective application in biomedical field, as the modified microspheres can reduce difficulties in embolization surgery.