Venous malformations (VM) are common vascular abnormality, and their management remains difficult. Pingyangmycin hydrochloride (PYM) is a useful sclerosant to treat venous malformations. This study was aimed to evaluate the effect of a new drug delivery system, PYM-loaded Zein/Zein-sucrose acetate isobutyrate (SAIB) in situ gels, in gelling and extending the local release of PYM. It was demonstrated that in vitro and in vivo release of PYM from the in situ gels could be extended up to 7 and 4 days, respectively. SAIB could significantly cut down the initial burst of PYM from the in situ gels (P<0.05). The possible gel forming and drug release mechanisms were described according to the morphology analysis by atomic force microscopy (AFM), optical microscopy and SEM. The gel forming efficacy and the viscosity of in situ gel solutions were satisfying.