There is evidence that PAR-2, cleaved and activated by tryptase, contributes to tumor progression in various cancer types. However, the role of PAR-2 in the context of myeloid leukemia remains unknown. In this study, we examined the role of PAR-2 activation on leukemic cell survival and proliferation using a human myeloid leukemia cell line (K562). Our study showed that PAR-2 was detected in K562 cells using RT-PCR. In a serum containing medium, K562 cells showed a significant increase in cell growth as determined by MTT assay. However, PAR-2 activating peptide (AP) SLIGRL-NH2 did not significantly alter cell growth when compared to controls. Using cleaved caspase-3 as a marker of apoptosis, cell culture with cycloheximide (CHX) (50 µg/ml) alone showed an increase in cell apoptosis. The PAR-2 AP alone did not alter K562 cell apoptosis. However, the effect of CHX on caspase-3 cleavage was significantly decreased in the present of PAR-2 AP, suggesting anti-apoptotic activity. Taken together, these results show that PAR-2 activation does not stimulate K562 cell proliferation. Instead, PAR-2 AP reduces K562 cell response to CHX-induced apoptosis. The results imply that enhanced tryptase levels during pre-leukemia may, via activating PAR-2, offer protection of tumor cells against chemotherapeutic agents thereby result in a survival advantage of the malignant clone. This work was supported by the Thailand Research Fund.