Implantable and poly (d,l-lactide-co-glycolide) (PLGA) microparticles were developed to deliver temozolomide (TM) continuously in interstitial chemotherapy for glioma. The therapeutic effect of temozolomide/PLGA was evaluated in a rat C6 glioma model. C6 cells were implanted orthotopically into 100 rat brains in 5 groups (n=20 each): sham operation group, control group, local delivery of blank PLGA microspheres group, oral TM group, and local delivery of TM/PLGA group. Rats in oral TM group were orally administered temozolomide, and rats in TM/PLGA group were locally implanted with TM/PLGA microspheres. Ten rats were selected randomly from each group for observing the survival time, and the other 10 rats were killed on POD 14 to measure proliferation activity and apoptosis of the gliomas. Head MRI examination was performed before the rats were killed. The median survival time of sham operation group, control group, blank PLGA microspheres group, oral TM group, and TM/PLGA group was 19.5, 20, 19, 27, and 46.5 days, respectively. MRI demonstrated that the tumor volume was reduced in oral TM group and interstitial TM/PLGA group. PCNA-positive cell staining showed that proliferation activity of tumor cells treated with interstitial TM/PLGA therapy significantly decreased when compared with that of tumor cells treated with oral TM therapy. The apoptosis of C6 cells in interstitial TM/PLGA group significantly increased when compared with that in oral TM group. Interstitial TM/PLGA was effective in treating intracranial C6 rat gliomas and could prove to be a potential chemotherapy agent for human malignant gliomas.