This study presents a chemical vapor sensor based on polymer-coated microsphere resonators. A theoretical simulation of the sensor response is performed, and optimization of the polymer layer thickness is investigated. Results show that the sensor exhibits a good linearity and a low detection limit of the refractive index change. Especially at the thermostable thickness of the polymer layer, the refractive index detection limit of the wavelength around 780nm can be as low as ~2 × 10ˉ⁸ refractive index unit for a spectral resolution of 10 fm, without any temperature control. Because of the good sensing performance and simple manipulation, the proposed sensor is a very promising platform for chemical vapor detections. © 2011 Optical Society of America.