The invention provides double-short-chain polyethylene glycol prodrugs of rapamycin and derivatives thereof, and application thereof. The double-short-chain polyethylene glycol prodrugs have water solubility of more than 10 mg/mL and overcome the problem of poor water solubility of RAPA; and short-chain MPEG has a molecular weight of 400 to 600, avoids safety problems which may brought by high-molecular-weight MPEG, has good safety and is applicable to parenteral administration.