Clinical observations have suggested that low-energy lasers might promote wound healing. Evidence suggests that He-Ne laser irradiation induces an increase in the rate of keratinocyte migration and proliferation as compared with nonirradiated controls in vitro. This study sought to determine whether He-Ne laser could induce cytokine production in cultured keratinocytes. The results revealed (i) a significant increase in interleukin-1 alpha and interleukin-8 production and their respective mRNA expression in He-Ne laser-treated groups as compared with nonirradiated controls, and (ii) under 1.5 joules/cm2 irradiation, this stimulating effect of He-Ne laser treatment is concentration-dependent. Because interleukin-1 alpha induces keratinocyte migration, this finding may partially explain the stimulatory effects on the motility of keratinocytes. As both interleukin-1 alpha and interleukin-8 provoke proliferation of keratinocytes, it is not unreasonable to propose that these two cytokines play a profound role in the enhancement of keratinocyte proliferation as a result of He-Ne laser irradiation. Our findings provide further evidence of enhanced wound healing at the cellular and molecular level as a result of the He-Ne laser.