Water soluble tacrolimus-mPEG conjugates have been synthesized and shown to be function in vitro as prodrugs. The desired 24-, 32- or 24, 32-esterified compounds were obtained by initially acylating of tacrolimus with iodoacetic acid at the 24-, 32-, or 24,32-positions and then reacting the resulting acylated tacrolimus with a mPEG in the presence of a base such as sodium bicarbonate. These conjugates were converted again into tacrolimus by the action of enzymes in human liver homogenate, and the half-lives of the conjugates are approximately 10min in the homogenate.