Abstract: The objective of this research was to investigate the effect of arm number of Poly(l-lactide)-b-methoxy poly(ethylene glycol) (PLL-b-MPEG) amphiphilic diblock copolymers on their characteristics of drug-loaded nanoparticles and in vitro drug release. Linear and star-shaped PLL-b-MPEG diblock copolymers were synthesized via the ring-opening polymerization of L-lactide followed by coupling reaction with a monofunctional carboxyl end-group MPEG. These diblock copolymers included linear copolymer having one arm and star-shaped copolymers having four and six arms. The crystallinity of MPEG block within diblock copolymers was suppressed. The melting point (Tm) and degree of crystallinity (χc) of PLL block within diblock copolymers decreased as the arm number increased. Drug-loaded nanoparticles of these copolymers were prepared by the emulsification-diffusion method under surfactant-free condition. Indomethacin was used as a poorly water-soluble model drug. The nanoparticles with less than 200 nm in size were nearly spherical shape. Different arm numbers did not affect average size and drug loading efficiency. However, the Tm and χc of diblock copolymers slightly decreased after drug loading. From in vitro drug release test, drug release content increased steadily as the arm number increased.