A new method based on micro-cantilever sensors was presented and used to investigate conformation transition of macromolecules. Poly(N-isopropylacrylamide)(PNIPAM)were grafted onto one surface of a micro-cantilever by self assemble monolayer method. Then the micro-cantilever was immersed into distilled water in which the temperature can be adjusted in the range of 20—40℃. The deflection of the micro-cantilever induced by conformation transition of PNIPAM chains was measured using optical lever technique. The results show that the micro-cantilever deflects upon heating and opposite deflection occurs upon cooling, which indicates that the surface stress of the micro-cantilever changes when the conformation of PNIPAM changes upon heating and cooling. The surface stress changes continuously over the range of 20—40℃. However, a sharp change appears around the low critical solution temperature (～32℃), at which a coil-globule transition occurs in free aqueous solution of PNIPAM. The whole process is irreversible and shows a clear hysteresis, which can be attributed to hydrogen bonding and the possible chain entanglement formed during the collapse process.