Photobiomodulation therapy (PBMT) is the application of a low-level laser device to generate physiological changes and provide therapeutic effects. Till now, the effects of PBMT on the neural differentiation of mesenchymal stem cells have been rarely reported. Herein, the potential effect and mechanism of PBMT on the neural differentiation of dental pulp stem cells (DPSCs) were preliminarily investigated in our research. The optimal dose of 3.75 J/cm(2) was first screened for use in the following neural-inducing studies. Then, DPSCs were cultured in neural induction medium and treated with laser irradiation for 7 days. From the results of morphology and immunofluorescence, we found that irradiation promoted the formation of neural stem cell-like spheroids derived from DPSCs and enhanced potential neural differentiation. Furthermore, neural differentiation gene expressions of Nestin, microtubule-associated protein-2, and neural cell adhesion molecule were increased after PBMT irradiation. The protein expressions of class III beta-tubulin and neurogenic differentiation factor 1 were also improved. Meanwhile, the involvement of extracellular signal-regulated kinase (ERK1/2) was investigated by western blot. Our study showed that the neural differentiation of DPSCs was promoted by PBMT, and the underlying mechanism in this process was associated with activating the ERK1/2 signaling pathway.