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Objective: To study the effect of oxymatrine on the expression of nuclear factor-kappa B(NF-κB) of Human benign epidermal keratinocytes line(HaCaT cells). Methods:HaCaT cells were cultured with different concentration of Oxymatrine(10 μ g/ml, 50 μ g/ml and 100 μg/ml) for 24 h, then 10-5 mol/L Substance P was added to the cells. After 30 rain, NF-κB expression in the cells was observed by immunocytochemistry, NF-κB P65 protein expression was evaluated by Western blot, and the mRNA expression of NF-κB P65 was evaluated by reverse transcription polymerase chain reaction(RT-PCR). The 10-5 mol/L Substance P and culture medium were added to the Substance P group and control group, respectively. Results:In control group, expression rate of positive cells, the expressions of protein and mRNA of NF-κB were all low. In Substance P group, when 10-5 mol/L Substance P was added, the expressions were all increased(P＜0.05). But in Oxymatrine groups, the expression rate of positive cells, the expressions of protein and mRNA were all descended in a concentration-dependent manner(P＜0.05 or P＜0.01 ). Conclusion:Oxymatrine can down-regulate the expression of NF - κB of the HaCaT ceils and may play an important role in regulating anti-inflammation and immunity.