Abstract: Objective To study the therapeutic effect of the combination of ultrasound irradiation and temozolomide-loaded hydrogel nanoparticle in the interstitial chemotherapy after surgical resection in a rat C6 glioma model,to observe the role in enhancing the effect of interstitial chemotherapy. Methods ①15 Wistar glioma rats after surgical resection were applied to test the diffusion of fluorescein-loaded hydrogel nanoparticles around the tumor cavity combined with ultrasound irradiation.The tumor residual cavity was filled with fluorescein-loaded hydrogel nanoparticle,divided randomlyinto three groups(n=5):no ultrasound group and ultrasound irradiation groups respective with 1 MHz 1 min 0.5 W/cm²and 1 MHz 1 min 1 W/cm²,on the seventh day,the brain tissues were collected and made frozen sections.The distribution of fluorescence were observed and photographed by fluorescence microscope,the fluorescence intensity was measured,and the difference offluorescence intensity was analyzed.②24 Wistar glioma rats were divided into four groups(n=6) randomly: Control group,operation group,operation+interstitial chemotherapy group,operation+interstitial chemotherapy+ultrasound group.The survival curves were obtained through the Kaplan-Meier method. Results In no ultrasound group,the fluorescein-loaded nanoparticle concentrated around the tumor cavity,and in ultrasound irradiation group,the fluorescein-loaded nanoparticle concentrated in the adjacent region,and diffused in the further brain tissue more effective.The survival difference among the therapeutic groups or compared with the control group was all statistically significance. Conclusion Ultrasound irradiation can enhance the diffusion of nanoparticle in hydrogel around the tumor cavity;ultrasound irradiation combined with interstitial chemotherapy containing temozolomide-loaded hydrogel nanoparticle will prolong the survival time of C6 glioma rat model after the surgical resection.