Photodynamic therapy using lisht emitting diodes (LEDs) and lasers has been shown effective for periodontal treatment. In previous research, we found that high‐intensity red LEDs promote hard tissue formation of human periodontal ligament stem cells and human bone marrow mesenchymal stem cells (BMSCs). On the other hands, it has been suggested that LED might induce cytotoxicity and inflammtion. Therefore, we investigated the biological effect of high‐intensity red LEDs on BMSCs, including cytotoxicity and inflammation. A high‐intensity red LED manufactured by Led Engin was used as a light source, and the irradiation energy was adjusted by changing the irradiation time. We performed cell proliferation and cytotoxicity assays, and examined the mineralization by alizarin red staining and the expression of IL‐6 and IL‐8. LED irradiation suppressed cell proliferation, and promoted cytotoxicity in an energy dose‐dependent manner at 48 hours of irradiation. The mineralization tended to be promoted most at 6J/cm2. LED irradiation promoted the expression of IL‐6 at 48 hours, and the expression of IL‐8 at 24 and 48 hours. In conclusion, high‐intensity red LED might promote the calcification of BMSCs, while promoting the cytotoxicity and gene expression of inflammatory cytokines. (J Osaka Dent Univ 2021; 55: 225‐230)