We have previously applied nuclear factor-κB bioluminescent imaging-guided transcriptomic analysis to assess host responses to biomaterials, ionizing radiation, and chemotherapy drug in vivo [21]–[23]. In this study, we applied PPAR bioluminescent imaging to evaluate the chitosan-affected metabolic responses. Microarray analysis of chitosan-targeted organs was further applied to globally elucidate gene expression profiles of chitosan and to find the novel mechanisms of chitosan. Our data showed that chitosan activated PPAR activities in brain and stomach. Additionally, chitosan regulated several pathways involved in lipid and glucose metabolism, which was in agreement with the well-known hypocholesterolemic and hypoglycemic effects of chitosan.