Optical fiber chemical sensing is generally achieved through attachment of sensor molecules to the fiber, a process that involves chemicals that are not biologically compatible or are limited to thin monolayer coatings. To address these limitations and enable in-vivo biosensing, we report here, for the first time, silk fibroin coating of optical fibers for encapsulating fluorescent sensor molecules. Silica exposed core fiber (ECF) samples were coated with a thin layer of silk – a naturally derived biopolymer composed entirely of proteins and amino acids. The silk was doped with the fluorophore 5,6-carboxynapthofluorescein (CNF), which allows optical measurement of pH by a robust ratiometric fluorescence method. The fluorescent signal from the doped-silk layer is coupled into the core of the ECF, enabling remote measurement of pH along the length of the fiber. We have demonstrated real time in vivo pH sensing measurements in a mouse model of hypoxia. Our results showed a continuous drop in the subcutaneous pH in the mouse lumbar area as hypoxia developed. The work explores, for the first time, the potential of a natural silk protein coating to perform fiber sensing inside the body.