OBJECTIVE To prepare the vincristine sulfate (VCR) microspheres by W/O/O solvent evaparation method and evaluate the effect of zinc carbonate (ZnCO3) on the morphology and release kinetics of the microspheres. METHODS Degradation kinetic of VCR was tested in PBS of four different pH values at 37TC to select the optimal incubation medium for in vitro release. Microspheres were made with or without Zn-CO3 (w/w 5% and 10%) in the polymeric phase. The properties and in vitro release profiles of the microspheres were examed. RESULTS ZnCO3 increased the stability of VCR in the PLGA microspheres. During the 36 days of in vitro release, the accumulative release of VCR from the microspheres reached > 70% when added with ZnCO3, and was (54.2 +/- 1.1)% when no ZnCO3 was added. 10% ZnCO3 showed superior effect than 5% ZnCO3 in the stabilization of microspheres. CONCLUSIONS Adding ZnCO3 is essential during the preparation of PLGA microspheres. It can remarkably improve the stability of drugs in the acid microenvironment inside PL-GA microspheres and decrease the VCR degradation during incubation.