Self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of insulin after oral administration, where insulin was complexed with phospholipid to achieve a better liposolubility in the form of insulin-phospholipid complex (IPC). IPC was formulated into the oil phase of SNEDDS by solvent-evaporation method. The formula of IPC-SNEDDS was optimized and characterized. Data showed that SNEDDS as a drug vehicle did not exhibit an obvious inhibition over MDCK cells, and it can facilitate the transport of IPC across MDCK cell monolayer. IPC-SNEDDS could enhance the absorption of insulin after oral administration and yielded a pronounced hypoglycemic effect on diabetic Wistar rats. All these suggested that IPC-SNEDDS has a great potential for oral delivery of insulin.