Purpose: Glioblastoma multiforme (GBM) is the most malignant brain tumor with the characteristics of highly infiltrative growth and recurrent rate. In this study, we used animal imaging and molecular expressive profiles to investigate the characteristics of the primary tumor (GBM-3) cells and recurrent tumor (S1R1) cells from different GBM patients. Procedures: Bioluminescent imaging and 3T magnetic resonance imaging (MRI) were used for assessing the orthotopical tumor development of GBM cells harboring a polycistronic reporter gene system. Western blot analysis and quantitative polymerase chain reaction were used to compare the molecular expressive profiles of two types of GBM cells. Results: S1R1 cells exhibited apparent invasive ability compared to GBM-3 cells using in vitro invasion assay. In vivo bioluminescent imaging showed that intracranial tumors are formed by both types of GBM cells, but the bioluminescent signal was also detected in the lumbar region at late-stage tumor formed by S1R1 cells. The MRI showed that intracranial tumors formed by S1R1 cells were highly infiltrative compared to that formed by GBM-3 cells. Additionally, these two GBM types expressed different patterns of molecules associated with tumor development. Moreover, the suppressive effects of interleukine-23 (IL-23) on xenograft tumors formed by both GBM types were detected using bioluminescent imaging. Conclusion: The current data suggest that the in vivo growth behaviors and therapeutic responses of the primary and recurrent human GBMs were comparable using the reporter gene imaging, and different molecular expressive profiles exist between these two GBM types.