The objective of this study was to prepare gliclazide-chitosan microparticles with tripolyphosphate by ionic crosslinking. Chitosan microparticles were produced by emulsification and ionotropic gelation. The effects of process variables including chitosan concentration, pH of tripolyphosphate solution, glutaraldehyde volume and release modifier agent such as pectin added to the tripolyphosphate crosslinking solution were evaluated. The microparticles were examined with scanning electron microscopy, infrared spectroscopy and differential scanning colorimetry. The serum glucose lowering effect of gliclazide microparticles was studied in streptozotocin-diabetic rabbits compared with the effect of pure gliclazide powder and gliclazide commercial tablets. The particle sizes of tripolyphosphate-chitosan microparticles were over the range 675-887 µm and the loading efficiency of drug was greater than 94.0%. In-vivo testing of the gliclazide-chitosan microparticles in diabetic rabbits demonstrated a significant antidiabetic effect of gliclazide-chitosan microparticles after 8 h that lasted for 18 h compared with gliclazide powder, which produced a maximum hypoglycaemic effect after 4 h. The results suggests that gliclazide-chitosan microparticles are a valuable system for the sustained delivery of gliclazide. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.