In the present study, we examined eye irritation oj six anti-wrinkle agents (ascorbic acid, glycolic acid, all trans-retinoic acid, ginseng extract, retinol, EB). We also compared eye irritation with skin irritation and cytotoxicity in HaCaT cells by these agents. The highest eye irritation was found in glycolic acid, but all trans-retinoic acid showed the highest skin irritation. The rank of eye irritation was not correlated with the cytotoxicity of agents. This result shows that eye irritation potency by these agents were not correlated with skin irritation potency, and cytotoxicity in HaCaT cells.