Tetragonia tetragonoides (Aizoaceae) has been known as an anti-cancer agent. The activation of proteinase-activated receptor-2 (PAR-2) by trypsin appears to play a role in inflammation. In the present study, we examined the inhibitory effects of Tetragonia tetragonoides water extract (TTWE) on the production of tumor necrosis $factor-{alpha};(TNF-{alpha})$ and tryptase in trypsin-stimulated human leukemic mast cells (HMC-1) expressing PAR-2. HMC-1 cells were stimulated with trypsin in the presence or absence of TTWE (10, 100, and $1000;{mu}g/ml$). The level of $TNF-{alpha}$ secretion from HMC-1 cells was measured by enzyme-linked immunosorbent assay (ELISA). $TNF-{alpha}$ and tryptase mRNA expression were examined by reverse transcription-PCR. Also, extracellular signal-regulated kinese (ERK) activation was assessed by Western blot analysis. Trypsin activity was measured using the substrate Bz-DL-Arg-p-nitroanilide (BAPNA). It was observed that $TNF-{alpha}$ secretion, tryptase mRNA and $TNF-{alpha}$ mRNA expression in trypsin-stimulated HMC-1 cells were inhibited by pretreatment of TTWE ($1000;{mu}g/ml$). Furthermore, the pretreatment of TTWE ($1000;{mu}g/ml$) resulted in the reduction of ERK phosphorylation and trypsin activity. These results suggest hat TTWE might have the inhibitory effects on the PAR-2-dependent inflammation processes and it is likely to function as PAR-2 antagonist.