This letter presents the first quantitative, in vivo, transcutaneous glucose measurements using surface enhanced Raman spectroscopy (SERS). Silver film over nanosphere (AgFON) surfaces were functionalized with a mixed self-assembled monolayer (SAM) and implanted subcutaneously in a Sprague-Dawley rat. The glucose concentration was monitored in the interstitial fluid. SER spectra were collected from the sensor chip through the skin using spatially offset Raman spectroscopy (SORS). The combination of SERS and SORS is a powerful new approach to the challenging problem of in vivo metabolite and drug sensing.