Abstract： Objective In order to improve the blood glucose(BG) lowing effect of polylactide acid microcapsulated insulin (PLA MCI),we changed the molecular weight of PLA,diameter of microsphere and observed the release profile of this new PLA MCI in PBS buffer,as well as the changes of peripheral BG in diabetic rats after feeding.Methods Release profile in vitro was made in PBS buffer,the insulin was measured by follin phenol method.In vivo the BG lowing effect of PLA MCI was studied in 4 groups of rats.Group 1 was normal rats ( n =6), group 2 was diabetic rats ( n =5),all these rats in both groups were fed by 2.4mg of pure insulin.Group 3 was diabetic rats ( n =10) fed by PLA MCI contained 2.4 mg of insulin.Group 4 was starve DM rats control group without any oral drug ( n =7).In the rats of 4 groups BG were measured every hour until BG returned to control level.The BG changes were compared among 4 groups.Results In vitro during 3～7h about 51.0%～73.4% of insulin had been released from PLA MCI.In vivo the maximum BG decreases were 31.0±15.1% in group 1,47.0±27.9% in group 2,40.0±16.7% in group 4 and 80.9±10.8% in group 3 during 13 hours.The BG lowing effect of PLA MCI began at 30 minutes,the peak times were in 1 to 3 hours after ingestion,the effect persisted for 10～12 hours.Under the scanning electron microscope the PLA MCI showed a intact shape but with many small hole surface after incubation in PBS and 1% lipase for 3 weeks.Conclusion By decrease of the molecular weight of PLA,and thinning wall of microsphere as well as increase of the diameter of microsphere,the insulin release rate was increased from PLA MCI, which also improved BG lowing effect in vivo after ingestion.Since PLA MCI still kept its slow degradation after 3 weeks,it may be in a good safety after ingestion.