In this paper, a surface plasmon resonance imaging (SPRI) system for cell analysis is developed for obtaining the surface plasmon resonance (SPR) signal from the interactions between cells and different stimuli. The system is constructed with a red laser light source, a P-polarizer, a glass prism, a 5× objective lens, a charge coupled device (CCD) camera, a gold sensor chip, a polydimethylsiloxane (PDMS) reaction well and a mechanical scanning device. The system is applied to mapping living cells in response to stimuli by characterization of the refractive index (RI) changes. Cell responses to K + in KCl solutions with concentrations of 5 mmol/L, 20 mmol/L, 50 mmol/L and 100 mmol/L are collected, which indicates that the SPRI method can distinguish the concentration of the stimuli. Furthermore, cell responses to epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) are studied independently. The binding of EGF receptor (EGFR) and EGF is collected as the first signal, and the internal change in cells is recorded as the second signal. The cell response to VEGF is different from that to EGF, which indicates that the SPRI as a label-free, real-time, fast and quantitative method has a potential to distinguish the cell responses to different stimuli.There are many conventional techniques for the evaluation of cell status, such as fluorescence microscopy, flow cytometry and electrical impedance. Most of the cell based assays require tedious labeling methods [1] which are time-consuming and may affect normal cell functions. The development of time-resolved label-free methodologies for the measurement of cellular properties is crucial for the analysis of living cells [2] .Surface plasmon resonance (SPR) is an extremely sensitive optical technique for the study of molecular interactions with advantages of real-time, label-free and kinetics detection at the sensor interface [3][4][5] . Recently, surface plasmon resonance imaging (SPRI), which is capable of spatially distinguishing refractive index (RI), was applied for real-time imaging of living cell activation [6][7][8] . Yanase et al [9] detected the RI changes in individual living cells by means of SPRI. Moreover, the SPR response could be used to describe cell growth [10] and evaluate the effectiveness of antitumor drug on tumor cells [11] . When cells were stimulated by extracellular stimuli via receptors, various intracellular events were initiated, which were then detected by SPR quantitatively [12] .In this paper, a homemade SPRI system is developed for cell analyses. SPR signals are obtained from the interactions between cells and different stimuli, such as K + , epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). This method provides a label-free, real-time, fast and quantitative way to detect RI changes in living cells induced by stimuli. The homemade SPRI system for living cell analyses is based on the prism coupling mode of the Kretschmann structure. As shown in Fig.1, the proposed SPRI system consists of a red la...