BACKGROUND AND OBJECTIVE: Infrared neural stimulation (INS) has recently evoked interest as an alternative to electrical stimulation. The mechanism of activation is the heating of water, which induces changes in cell membrane potential but may also trigger heat sensitive receptors. To further elucidate the mechanism, which may be dependent on cell type, a detailed description of the temperature distribution is necessary. A good control of the resulting temperature during INS is also necessary to avoid excessive heating that may damage the cells. Here we present a detailed model for the heating during INS and apply it for INS of in vitro neural networks of rat cerebral cortex neurons. STUDY DESIGN/MATERIALS AND METHODS: A model of the heating during INS of a cell culture in a non-turbid media was prepared using multiphysics software. Experimental parameters such as initial temperature, beam distribution, pulse length, pulse duration, frequency and laser-cell distance were used. To verify the model, local temperature measurements using open pipette resistance were conducted. Furthermore, cortical neurons in culture were stimulated by a 500? mW pulsed diode laser (wavelength 1,550? nm) launched into a 200 ?µm multimodal optical fiber positioned 300? µm from the glass surface. The radiant exposure was 5.2?J/cm(2) . RESULTS: The model gave detailed information about the spatial and temporal temperature distribution in the heated volume during INS. Temperature measurements using open pipette resistance verified the model. The peak temperature experienced by the cells was 48°C. Cortical neurons were successfully stimulated using the 1,550 ?nm laser and single cell activation as well as neural network inhibition were observed. CONCLUSION: The model shows the spatial and temporal temperature distribution in the heated volume and could serve as a useful tool for future studies of the heating during INS.