In the present study we aimed to control insulin release from the reverse hexagonal (HII) mesophase using Thermomyces lanuginosa lipase (TLL) in the environment (outer TLL) or within the HII cylinders (inner TLL). Two insulin-loaded systems differing by the presence (or absence) of phosphatidylcholine (PC) were examined.In general, incorporation of PC into the HII interface (without TLL) increased insulin release, as a more cooperative system was formed.Addition of TLL to the systems’ environments resulted in lipolysis of the HII structure. In the absence of PC, the lipolysis was more dominant and led to a significant increase in insulin release (50% after 8h). However, the presence of PC stabilized the interface, hindering the lipolysis, and therefore no impact on the release profile was detected during the first 8h.Entrapment of TLL within the HII cylinders (with and without PC) drastically increased insulin release in both systems up to 100%. In the presence of PC insulin released faster and the structure was more stable.Consequently, the presence of lipases (inner or outer) both enhanced the destruction of the carrier, and provided sustained release of the entrapped insulin.