Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades.However,its application is greatly limited by its extremely short half-life in vivo,poor membrane permeability and extensive metabolism in gastrointestinal tract,resulting in repeated injection and poor patient compliance.In the present study,we developed a TP5-loaded,phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and longlasting therapeutic effects.We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition.Moreover,the PPSG exerted a low cytotoxicity in L929 cells and HUVECs,suggesting the biocompatibility of PPSG.A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo,revealing its sustained and controlled drug release property.Most importantly,in cyclophosphamide-induced immunosuppressive rats,a single dose of TP5 PPSG (15 mg/kg,sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio;such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day,sc) for 14 consecutive days.Thus,TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process,good biocompatibility and long-lasting immunomodulatory efficacy,which could greatly improve patient compliance.