Background The elevated matrix metalloproteinase (MMP) activity is an important cause of chronic wound healing failure.Arsenolite,whose main component is arsenic trioxide (As2O3),iS a common traditional Chinese medicine wildly used in treating chronic wounds; it can remove necrotic tissue and promote tissue regeneration.This research was designed to evaluate the effects of AS2O3 on production and activities of MMP-1,MMP-2 and MMP-9,and on regulation of its signal transduction pathway in human skin fibroblasts (HSFb) and human monocyte line (THP-1 cells) that were in an inflammatory state.Methods We established three cell models; HSFb activated by TNF-α,THP-1 cells activated by phorbol 12-myristate 13-acetate (PMA) and an HSFb-THP-1 co-culture system.Three cell models was cultured with As2O3 for 24 hours.The levels of MMP-1,MMP-2,MMP-9,TNF-α and IL-β in the cell culture supatants were assayed by ELISA.The mRNA expressions of MMP-1,MMP-2 and MMP-9 were determined by RT-PCR.The activities of MMP-2 and MMP-9 were tested by Gelatin zymography assays.The phosphorylation levels of ERK1/2 and p38MAPK were assayed by West blotting.Results As2O3 inhibited the expression of MMP-1,MMP-2 and MMP-9 mRNA,the secretion and activity of MMP-1,MMP-2 and MMP-9 in HSFb and THP-1 cells in the inflammatory state (P ＜0.05 and P ＜0.01 respectively).It also inhibited the secretion of TNF-α and IL-1β in THP-1 cells and in the co-culture system (P ＜0.05 and P ＜0.01,respectively).It also decreased the phosphorylation of ERK1/2 and p38 MAPK in HSFb and THP-1 cells (P ＜0.05 and P ＜0.01,respectively).Conclusions As2O3.as a main component of arsenolite,can inhibit the production of MMPs by HSFb and THP-1 cells in an inflammatory state through inhibiting the release of inflammatory factors and the activation of the MAPK cascade pathway.This may be a possible mechanism for arsenolite healing chronic wounds.