The invention discloses an oral PEGylated 
insulin pH-sensitive naonparticle and a preparation method thereof. The naonparticle is prepared from PEGylated 
insulin, pH-sensitive 
polymer, carrier, additives and stabilizer. The preparation method of the naonparticle comprises the following steps: preparing a PEGylated 
insulin / pH-sensitive 
polymer / carrier W / O primary 
emulsion, dispersing the W / O primary 
emulsion in a stabilizer solution to form a W / O / W multiple 
emulsion, obtaining a crude product after the 
solvent volatilizes, purifying the crude product, and carrying out freeze-
drying to obtain the naonparticle. The PEGylated insulin pH-sensitive naonparticle disclosed by the invention has the advantages of uniform dispersion and high 
medicine enveloping rate; the insulin modified by 
polyethylene glycol can reduce the aggregation of insulin molecules, prolong the 
half life in vivo, and prolong the time of 
blood sugar reduction effect; and the release rate of the insulin in the 
gastric acid environment is reduced, the release rate of the insulin in the intestinal tract environment is enhanced since the naonparticle swells, and thus, the oral PEGylated insulin pH-sensitive naonparticle has an 
oral application value.