A Helium-Neon (He-Ne) laser with a wavelength of 632.8 nm is known to have photobiological effects and is widely used for reducing the pain of herpes zoster and accelerating wound healing, however the cellular mechanism and effect of the He-Ne laser are poorly understood. The present study was designed to examine the influence of He-Ne laser irradiation on irritant and allergic contact dermatitis of the mouse ear and on histamine release from rat peritoneal mast cells. Irradiation was applied with a He-Ne laser (12.2 J/cm2) at 1 h, 10 min, 5 min and 0 min before, and 5 min, 6 hs and 24 hs after a challenge of an irritated contact dermatitis (ICD) or allergic contact dermatitis (ACD) was made on the right ears of ICR-mice. Twenty-four hours after the challenge, the swelling of the ear was measured with a dial thickness gauge, and the anti-inflammatory effect of He-Ne laser irradiation was expressed as an ear thickness ratio (ETR). Although the laser did not decelerate the ETR from ICD, the allergic response was decelerated. Irradiation at 5 min after the challenge of contact dermatitis increased the thickness ratio. Next, the influence of the He-Ne laser on histamine release from Wistar-rat peritoneal mast cells was observed. The spontaneous histamine release was inhibited by laser irradiation, while substance P and compound 48/80-induced histamine release were not inhibited. From these results, it can be suggested that He-Ne laser irradiation has an anti-inflammatory effect on cutaneous inflammation.